“Anti-Tau Drugs for PSP Move into Phase II”

There’s not much new here from this report from last week’s Movement Disorder Society conference in Vancouver.  This report focuses on two anti-tau drugs being studied in PSP — one from AbbVie and one from Bristol-Myers Squibb.  The BMS drug was recently licensed to Biogen.  Both drugs proved safe in phase I studies, and both have moved into phase II trials.

Tau is the protein involved in PSP and CBD.  It’s one of two proteins involved in Alzheimer’s.

Here’s a link to the report:  (you have to register — no charge to do so — at Medpage Today to read the article)

https://www.medpagetoday.com/meetingcoverage/mds/65883

Meeting Coverage > MDS
Anti-Tau Drugs for PSP Move into Phase II
But phase I study of one agent pulled from presentation
by Kristina Fiore, Deputy Managing Editor, MedPage Today
June 08, 2017

June 2017 Parkinson’s Support Group Meetings – Guest Speakers – NorCal + Central CA

Here’s a list of guest speakers at many Northern California and Central California PD support group meetings for June 2017.

With my Brain Support Network atypical parkinsonism (DLB, PSP, MSA, CBD) hat on, these meetings are especially appealing to me (because of the guest speakers or topics) BUT remember that these are PD support group meetings:

Santa Rosa, Sat 6/3:  Neurologist speaks about mood, cognitive, and sleep disorders in PD.  This might be applicable to those with DLB and MSA.

Roseville, Tues 6/6:  Learn from a pharmaceutical company rep about a new drug for hallucinations and delusions.  This is applicable to those with DLB.

Sonoma/Vintage House, Thurs 6/8:  Topic is balance and fall prevention.  Speaker unlikely to know about any of the atypical parkinsonism disorders specifically but she probably has some good suggestions.

Stockton, Thurs 6/8:  Medical marijuana is the topic

Gilroy, Mon 6/12:  Listening to and discussing Michael J. Fox Foundation podcasts on sleep disturbances and urinary problems in Parkinson’s.  This is applicable to those with DLB and MSA especially.

Pacific Grove (Monterey County), Tues 6/13:  Speech therapist talks about speech and swallowing changes in PD.  This is applicable to all the disorders in our group.

Palo Alto Young Onset Parkinson’s Group Tues 6/13:  Medical cannabis is the topic

Palo Alto/Avenidas, Wed 6/14:  Manager of Stanford’s Farewell to Falls program will be speaking on the topic of fall prevention.  This is applicable to everyone in our group, whether you can take advantage of Stanford’s program or not.

Sacramento/Arden Arcade, Thurs 6/15:  Movement disorder specialist Lin Zhang, MD, PhD will be addressing the non-motor symptoms of PD.  These symptoms are part of the disorders in our group.

Mill Valley, Fri 6/13:  Registered dietitian speaks about nutrition and PD.  Most of the information should be applicable to those in our group.

Fremont, Mon 6/26:  Movement disorder specialist Han Lee, MD will be the guest speaker.  Unfortunately we don’t know his topic.  But he is very familiar with all the disorders in our group.

Generally, I recommend driving no more than 30 minutes to attend any of these meetings.  If you attend a meeting and learn anything, please share with me so that I can share with others!

Do you need to know the support group meeting location, day/time, contact info, and how to RSVP if required?  Please refer to the Stanford
Parkinson’s website for all Northern and Central California support groups:

parkinsons.stanford.edu/support_groups.html

As always, I’ve deleted the deep brain stimulation-related talks.

Robin

**********************

Half Moon Bay
Thursday, 6/1, 3-4pm
Guest Speaker:  Cherry Tuck, PD fighter
Topic:  Her journey
RSVP?:  No.

San Jose/Willow Glen
Friday, 6/2, 10am-noon (program starts about 10:20am)
Program:  Break into two groups — those with PD and caregivers
RSVP?:  No.

Santa Rosa (Sonoma County)
Saturday, 6/3, 1-3:15pm  (guest speaker 1-2pm)
Guest Speaker:  Allan Bernstein, MD, neurologist, Santa Rosa
Topic:  Mood, cognitive, and sleep disorders in Parkinson’s
RSVP?:  No.

Lodi
Monday, 6/5, 10-11am
Guest Speaker:  Dianna Powell, San Joaquin County coordinator, Legal Services of Northern California
Topic:  HICAP and Medicare updates
RSVP?:  No.

Roseville
Tuesday, 6/6, 1:30-3pm
Guest Speaker:  Saul Avila, Acadia Pharmaceuticals
Topic:  Nuplazid – new drug for psychosis and schizophrenia associated with Parkinson’s
RSVP?:  No.

San Francisco/UCSF Young Onset Parkinson’s Group
Tuesday, 6/6, 6:30-8pm
Guest Speaker:  Cameron Wisdom, Mission Bay Rock Steady Boxing Gym, San Francisco
RSVP?:  Yes, preferred to Monica Volz, [email protected]

Soquel (Santa Cruz County)
Wednesday, 6/7, 1-2:30pm
Guest Speaker:  Jenifer Armstrong, PharmD, pharmacist, Santa Cruz
Topic:  PD – Inside and out of the prescription bottle
RSVP?:  No.

Chico
Wednesday, 6/7, 1:30-3pm
Guest Speaker:  Attorney, Corporon Law Offices
Topic:  Long-term care planning (trusts, wills, and other legal documents)
RSVP?:  No.

Sonoma/Vintage House
Thursday, 6/8, 10-11am
Guest Speaker:  Vanessa Kettler, balance instructor
Topic:  Balance and fall prevention
RSVP?:  No.

Stockton
Thursday, 6/8, 1:30-3pm
Guest Speaker:  Christopher Trinchera
Topic:  Medical marijuana
RSVP?:  No.

St. Helena/Rianda House  (new group)
Thursday, 6/8, 3:30-4:30pm
Guest Speaker:  Barbara Brown, PT, physical therapist, St. Helena Hospital
Topic:  Importance of a PT’s expertise in a PD care plan
RSVP?:  No.

Fresno
Saturday, 6/10, 10am-noon
Guest Speaker:  Beate Ritz, MD, PhD, UCLA
Topic:  PEG (Parkinson’s, Environment & Genes) study at UCLA
RSVP?:  No.

Yuba City (Tri-Counties)
Monday, 6/12, 1-2pm
Guest Speaker:  Carly Pacheco, deputy director, FREED Center for Independent Living, Grass Valley
Topic:  FREED Center’s services
RSVP?:  No.

Gilroy
Monday, 6/12, noon-1:30pm (new time)
Program:  Listening to and discussing Michael J. Fox Foundation podcasts on sleep disturbances and urinary problems in Parkinson’s
RSVP?:  No.

Bakersfield
Tuesday, 6/13, 2-4pm
Guest Speaker:  Lin Zhang, MD, PhD, movement disorder specialist, UC Davis, Sacramento
Topic:  PD and the management of off episodes with Apokyn
RSVP?:  Yes to group leaders Linda Feist, 661-304-9227, or Bill Burgemaster, 661-343-2707

Pacific Grove (Monterey County)
Tuesday, 6/13, 3-4:30pm
Guest Speaker:  Katie Pietsch, SLP, speech therapist, CHOMP
Topic:  Think LOUD! – Speech and swallowing changes in PD
RSVP?:  No.

Palo Alto Young Onset Parkinson’s Group
Tuesday, 6/13, 6:30-8pm
Guest Speaker:  Helen Garvy, PD advocate and care partner
Topic:  Medical cannabis for PD
RSVP?:  Preferred, if this is your first time.  RSVP at least 24 hours in advance to Martha Gardner, group leader, email [email protected]

Turlock
Wednesday, 6/14, 1-2pm
Guest Speaker:  Robert McCulla, DDS, dentist
Topic:  Parkinson’s and sleep
RSVP?:  No.

Palo Alto/Avenidas
Wednesday, 6/14, 2-3:30pm
Guest Speaker:  Ellen Corman, manager, Farewell to Falls, Stanford Health Care
Topic:  Fall prevention in Parkinson’s
RSVP?:  No.

Sacramento/Arden Arcade
Thursday, 6/15, 10am-noon
Guest Speaker:  Lin Zhang, MD, PhD, movement disorder specialist, UC
Davis, Sacramento
Topic:  PD – more than motor symptoms
RSVP?:  No.

Walnut Creek (Mt. Diablo)
Saturday, 6/17, 9am-noon  (speaker 10:45am-11:45am)
Guest Speaker:  Nijee Luthra, MD, PhD, movement disorders fellow, UCSF
Topic:  Advances in treatment of Parkinson’s
RSVP?:  No.

Lincoln
Tuesday, 6/20, 10-11am
Guest Speaker:  Millie Nunez, PD cycling instructor, Sun City Lincoln Hills
Topic:  Nutrition and forced exercise
RSVP?:  No.

Auburn
Tuesday, 6/20, 1:30-3pm
Guest Speaker:  Stephanie Fiola, RN, AbbVie Pharmaceuticals
Topic:  Discovering Duopa – carbidopa/levodopa eternal suspension
RSVP?:  No.

Modesto
Wednesday, 6/21, 1:30-3:30pm
Guest Speaker:  Carlos Becerra, personal trainer, Alpha Fitness
RSVP?:  No.

Auburn (special bonus meeting at same location as regular meeting)
Thursday, 6/22, 6-7:30pm
Guest Speaker:  Robert Ghelfi, MD, Northern California Surgical Group, Redding
Topic:  Stem cell therapy for PD
RSVP?:  No.

Mill Valley (Marin County)
Friday, 6/23, 1-3pm  (guest speaker 1-2pm)
Guest Speaker:  Sue Weiss, RD, dietitian, Kaiser San Rafael
Topic:  Nutrition and Parkinson’s
RSVP?:  No.

Fremont
Monday, 6/26, 7-9:30pm
Guest Speaker:  Han Lee, MD, movement disorder specialist, Kaiser San Leandro
RSVP?:  No.

Short descriptions of four atypical parkinsonism disorders on MJFF website

Looks like this webpage on the four atypical parkinsonism disorders — CBD, LBD, MSA, and PSP — was recently created on the Michael J. Fox Foundation website.  (It wasn’t there in July 2016, when we became one of their partners.)  Here’s a link to the new webpage:

www.michaeljfox.org/understanding-parkinsons/living-with-pd/topic.php?atypical-parkinsonism

Below, I’ve copied the summaries of the four disorders from the short webpage.  In addition to these summaries, the webpage also discusses treatment for these diseases.

Robin
—————————–

Excerpts from

Atypical Parkinsonism
Michael J. Fox Foundation Webpage
Un-dated

Corticobasal Degeneration (CBD)
Corticobasal degeneration (CBD) leads primarily to motor and cognitive (memory/thinking) symptoms. Motor symptoms mainly affect one arm and/or hand and include:
* slowness,
* stiffness,
* myoclonus (rapid muscle jerks), and
* dystonia (an abnormal, fixed posture).

The dystonic posture may cause the arm to be held close to the body and bent at the elbow and the wrist and fingers to be flexed toward the palm. Dystonia can cause pain and palm sores and interfere with regular daily activities (such as brushing teeth or preparing meals). Cognitive problems can affect speech, memory and/or behavior. Brain-processing difficulties can make performing complex motions, such as combing hair or turning a key in a lock, challenging or impossible. People with CBD may also experience “alien limb phenomenon,” which is involuntary activity of a limb and a feeling that the limb is foreign or has a will of its own. (An alien hand could take one’s eyeglasses off after the other hand has put them on, for example.)

Lewy Body Dementia (LBD)
Lewy body dementia (LBD), also known as dementia with Lewy bodies (DLB) is a form of dementia associated with PD, typically occurring early in the course of disease. LBD involves motor symptoms of Parkinson’s (usually stiffness and slowness) and significant impairment of thinking and/or memory abilities that interferes with daily activities. Additional symptoms may include:
* visual hallucinations (seeing things that aren’t there),
* unpredictable fluctuations in levels of alertness or attention, and
* mood, behavioral and/or personality changes.

REM sleep behavior disorder, in which a person acts out his or her dreams, and orthostatic hypotension (a decrease in blood pressure when changing positions that can cause dizziness or lightheadedness) are other common symptoms.

Multiple System Atrophy (MSA)
Multiple system atrophy (MSA) patients may experience:
* parkinsonism — usually slowness, stiffness and walking/balance difficulties (rather than tremor);
* cerebellar symptoms — incoordination, imbalance and/or slurred speech; and
* autonomic nervous system dysfunction — problems with the body’s automatic activities such as blood pressure regulation, bladder emptying and sexual functions.

Other features of MSA include abnormal postures (head and neck tilted forward, hand held in a grasping position, or foot and ankle turned inward); speech and swallowing problems; episodes of uncontrolled laughter or crying (pseudobulbar palsy); cognitive (memory/thinking) problems; and sleep disturbances, including REM sleep behavior disorder (acting out one’s dreams) or sleep apnea (breathing pauses during sleep).

Progressive Supranuclear Palsy (PSP)
Progressive supranuclear palsy (PSP) causes imbalance, gait difficulties and a tendency to fall backwards. It also restricts normal eye movements, which can lead to reading difficulties, falls when walking down stairs and visual disturbances (blurred or double vision, or light sensitivity). Involuntary eyelid closure (called blepharospasm); memory and behavior changes (such as decreased motivation and emotional fluctuations); and speech and swallowing problems also may occur.

Urinary Problems in PD – Webinar Notes

The Michael J. Fox Foundation (michaeljfox.org) hosts webinars every third Thursday on various Parkinson’s Disease (PD) topics.  The April 2017 hour-long webinar was on urinary symptoms in PD.  The speakers addressed how PD affects the autonomic nervous system, including bladder functions; how urinary problems are diagnosed and managed; and the latest in research.

Certainly many in the Brain Support Network community cope with urinary symptoms.  During the webinar, alpha-synuclein is mentioned.  Both multiple system atrophy and Lewy body dementia are disorders of alpha-synuclein.

The webinar recording is available online here:

www.michaeljfox.org/understanding-parkinsons/webinar-registration.php?id=23&e=1389435&k=8EDACA15229E6F2DA1A8C61247716FDD

(You’ll need to register first to obtain access to the recording.)

Brain Support Network volunteer extraordinaire Denise Dagan listened to the webinar and took notes.  Her notes are copied below.

Sorry but the Fox Foundation doesn’t announce its webinar presenters in advance, and that information is not posted to its website.  So I’m unclear who all the presenters were.  One of the presenters is Dr. Maria De Leon, is a retired movement disorder specialist who also has Parkinson’s Disease.   Other presenters were Dr. Miyasaki and Dr. Juncos.  The moderator is always Dave Iverson, a journalist who has PD.

Robin

—————————–

Denise’s Notes

Urinary Problems in Parkinson’s Disease
Michael J. Fox Foundation Webinar
April 20, 2017

The Autonomic Nervous System Controls the Body’s Automatic Functions:
* Blood pressure
* Heart rate
* Temperature
* Digestion
* Sexual function
* Bladder control

Constipation can affect bladder control.  Urinary and sexual function are under treated because symptoms are attributed to aging, rather than to Parkinson’s disease.

Autonomic Problems are Common in Parkinson’s:
* Up to 80% of people with PD may experience an autonomic symptom during their disease course.
* Autonomic symptoms are likely due to the underlying disease process of Parkinson’s, but can be worsened by certain PD and other medications.
* The protein alpha-synuclein, which misfiles in PD, may play a role in autonomic dysfunction.

Alpha-synuclein not only collects in, and damages, the brain, but affects the periphery of the nervous system as well (ganglia and nerve roots of the autonomic nervous system) leading to the degeneration of those nerves.  Most of the symptoms caused by this degeneration can be managed, including by PD meds that treat motor symptoms.  Sometimes these meds make autonomic symptoms worse.  Tell your Dr. so he/she can adjust meds for best autonomic symptom treatment.

In general non-motor symptoms tend to cluster together.  Over time people accumulate more non-motor symptoms, including autonomic symptoms.  There needs to be a balance of symptom treatment with medications -vs- side-effects of those medications.

PD Urinary Problems May Include Difficulty Holding or Emptying Urine:
The bladder stores and empties urine.  In Parkinson’s, the brain’s control of the bladder is disturbed.
* Difficulty holding ruing may lead to:
— Strong urges to urinate
— Increased frequency of urination, especially at nighttime
— Accidental loss of urine (incontinence)
* Difficulty emptying urine could cause:
— Hesitancy when starting urination
— Weak stream
— Feeling of incomplete bladder emptying
* Difficulty holding and emptying urine can lead to urinary tract infections.

Dr. DeLeon initially experienced increased urgency.  10 years into her diagnosis she has discovered it is not one single factor causing bladder problems.  Not just worsening PD, or needing medication adjustment, but aging, diabetes, prostate enlargement, etc., comes into play.

Most common urinary symptoms in PD:
* Irritative symptoms – noctural frequency, daytime urgency, incontinence (leaking), daytime frequency
* Obstructive symptoms – hesitancy, poor flow, incomplete emptying
* Aging contributes to all of these symptoms.

How do you sort out what’s caused by PD and what’s due to aging, enlarged prostate, etc.?
* Best practice in diagnosis is building a multidisciplinary team to determine what is going on with the patient.
* Uro-dynamics is a test whereby the bladder is filled and its function is monitored.
– In overactive bladder any amount of content causes contraction, urgency, therefore frequency.
– In obstructive bladder there is difficulty in flow.  When caused by enlarged prostate, it can be treated with meds and/or surgery.
* Treatment begins with least invasive to more invasive.

Have an open conversation with your physician about urinary issues because most symptoms have a treatment if the cause can be determined.  Patients should not assume new urinary difficulties are associated with PD and/or aging, but mention it to your doctor and be persistent, especially if it becomes a quality of life issue for yourself or your caregiver/family.  Keep track of your urinary behaviors and symptoms to best help your doctor(s) determine the cause of your bladder and constipation issues.

(Dr. DeLeon found her constipation was causing bladder obstruction, so treating the constipation eased bladder issues).

Another issue is difficulty with movement impeding getting to the toilet in time, getting clothing closures undone in time, etc. due to increasing PD symptoms.

Listener question about his mother having frequent urinary tract infections.  In reply, an MD says incomplete emptying of the bladder is common in people with PD due to improper functioning of the bladder muscles, especially in older men due to enlarged prostate. Leaving urine in the bladder is the perfect medium for bacterial growth and resulting in frequent urinary tract infections (UTI). These can be treated with antibiotics, even chronic prophylactic antibiotics (although this puts you at risk of antibiotic resistance), and surgical intervention.  Elderly people can not realize they have a UTI, which can adversely affect PD symptoms, PD medications don’t work as well, and seem just as though they are having a bad day because the older you are the less prominent the symptoms of s UTI.  Systemic UTI (beyond the bladder) can cause confusion, hallucinations, and ER visits.  Because of this, UTI must be in the fore of your mind when and older person with PD is feeling under the weather.

Treatment Targets the specific Urinary System:
Difficulty holding urine
> Non-pharmacologic
– Pelvic floor exercises
– Limit fluids/caffeine, schedule bathroom breaks, use incontinence aids
> Pharmacologic
– Medication to relax the bladder
– Botulinum toxin injections

Difficulty eliminating urine
> Pharmacologic
– Medication to stimulate bladder emptying
– Evaluate current drugs to ensure none contribute (e.g., Artane/trihexiphenidyl)
> Non-pharmacologic
– Intermittent catheterization

* Consider seeing a urologist or other doctor with expertise in the urinary system to compete urodynamic testing and determine if symptoms are from Parkinson’s or other issues.

* Tracking symptoms can be useful in managing these problems.

Listener question: How do PD meds complicate urinary problems, particularly frequency?  MD answer:  Generally, PD meds do not cause bladder problems.  Used to use anti-cholinergics (for people with tremor), including Amantadine, which can result in urinary retention or inability to void.  Other meds for non-motor symptoms, like depression (Mertazapine) has anti-cholinergic affects, as well.

Also, low blood pressure during the day can result in having to get up frequently at night to pee because sitting and standing the kidneys don’t have high enough blood pressure to produce urine, and laying down at night increases blood pressure and allows kidneys to produce urine and fill the bladder.

How does one reconcile conflicting advice about staying hydrated to maintain blood pressure, and limiting fluids to compensate for difficulty in holding one’s urine?  Fluids help with constipation, which affects your ability to void.  After 6:00pm don’t drink a lot of fluids to minimize nighttime urination.

Dr. DeLeon contributes fluids are especially important during the hot months of the year, but during the daytime.  Also avoid caffeine, chocolate, and spicy foods which can all make you pee more often.

Pelvic floor exercises are often prescribed for women with respect to birth.  Try to stop the stream while you pee to find the muscles to exercise.  Don’t do this while you pee to prevent urine retention and UTIs.  Both men and women should do this exercise several times to a count of 10 throughout the day to strengthen pelvic floor muscles.  This prevents leakage and helps to void completely.

What medications can be helpful?
– What can be aggravating the situation so can be eliminated or modified to improve the situation, especially diuretics, opioids, amantadine, anti-cholinergics, calcium channel blockers.  Work with the physician team to adjust medications.
– Other medical conditions that can aggregate bladder symptoms, like BPHD, atrophic vaginitis, prior abdominal surgeries, how many children you have had, sleep disorders, diabetes, venus insufficiency, etc.
– Medications to help the bladder relax or minimize irritation and contracting before getting to the toilet.  These are anti-cholinergics but not those that stimulate the bladder.  There are many choices, like Detrol, or Vesicare, which has been studied on PD patients.  There are potential side-effects.  Beta3 receptor, Myrbetriq, works but may cause high blood pressure.
– Medications to improve emptying by relaxing the sphincter (Flomax, Rapiflow) and reducing the size of the prostate.  Some of these drop blood pressure more than others.
– In PD patients with motor fluctuations, minimizing OFF periods reduces urge to empty the bladder, especially when one cannot move well.

Dr. DeLeon commented about what’s been most helpful, personally. Many women tend to have greater risk of UTI and urgency from taking Azilect, but it helps her with pain so she has to find a way to work around balancing symptom treatment.  She was taking Myrbetriq and anti-spasmotic, but everything (even behavior therapy) only helps for awhile.  Dopamine can inhibit release of insulin and found she was becoming insulin resistant.  Even though she is not diabetic, she is on blood sugar medication, which stopped her bladder problems and she was able to stop taking Myrbetriq.

Dave asked Dr. Miyasaki about connection between blood sugar levels and bladder issues.  There is a close connection between the brain and the gut, including the pancreas.  Adding an endocrinologist to your care team is warranted.  PD patients have an increased risk of diabetes, statistically, but the reason is unknown.  Some diabetes meds increase kidney excretion of glucose resulting in urinary frequency.

Ongoing Research into Urinary Problems and Parkinson’s
* Trials are investigating the brain mechanisms involved in overactive bladder, as well as varied treatments.
> Medications = e.g., Melatonin
> Behavioral modifications = pelvic floor exercises, and Bladder routine/schedule
> Transcutaneous electrical nerve stimulation = Non-invasive stimulation of lower leg nerves through skin device.

Dr. Miyasaki agrees that starting with the least invasive treatments is wise.  Melatonin has multiple benefits to patients, especially for sleep.  It is difficult to determine the benefit of behavior modifications, but they are not harmful and can be beneficial so they are worth a try.  There are reports that transcutaneous electrical nerve stimulation help with both frequency and difficulty emptying.  People with PD can have a less common disorder where the sphincter of the bladder will not relax.  It can be quite painful and risks UTIs.  People who have had DBS report better sleep and less urinary frequency, especially at night.

Q&A
More questions about how much fluid and when it should be consumed?
8oz, 6-8 times daily until 6:00pm – depending on whether you are taking diuretics.

Any connection between bladder problems and development of kidney stones?
If you’re not able to void regularly you may develop kidney stones, but they have more to do with your body eliminating various minerals or whether you’ve had repeated infections.  If you are well hydrated, kidney stones shouldn’t be a problem.

Dr. Miyasaki feels strongly that your neurologist is connected with other specialists so each patient has a multidisciplinary care team, especially those who are interested in treating Parkinson’s disease within their specialty, like urology, and see a volume of patients to really develop an expertise in treating Parkinson’s patients overall.

Dr. Juncos doesn’t want people to forget Botox can be tremendously beneficial to urinary treatment (and other non-motor symptoms) in Parkinson’s disease and can be used repeatedly.  Also, men are offered prostate surgery to reduce urinary obstruction, but that will not treat the autonomic symptoms, so what level of benefit can they expect from the surgery?  Ask a lot of questions before you do the surgery.

Dr. DeLeon reminds people there are many treatment options for urinary issues and there is no reason to be embarrassed.  Bring it up with your doctor and be patient in determining the problem and treatment.  Keep the symptom diary for ALL PD symptoms.  It is infinitely useful in your own PD care.

A protein called PERK may be a target for PSP, CBD, and other tauopathies

Brain Support Network will very likely be hosting and organizing a PSP/CBD conference in San Francisco in October.  (Stay tuned….) One of the international researchers we’ll be inviting to speak is Gunter Hoglinger from Munich.  He’s been involved in PSP and CBD genetics research for at least a decade.  Very impressive guy.

I was looking up a bit about Dr. Hoglinger online and came across this Science Daily article based on a press release from early February 2017 about research published by him and the German Center for Neurodegenerative Diseases (DZNE).  This is basic research using donated brain tissue, cell cultures, and mice.  This basic research can be the basis of good clinical trials down the road.

Here’s an excerpt from the Science Daily article:

“In previous studies, Höglinger and his colleagues had found that the risk for PSP is associated with variants at the PERK [protein kinase RNA-like endoplasmic reticulum kinase] gene, and that loss of PERK function induces tau pathology in humans. For the current study, they examined the functioning of this protein more closely, to see how its effects could be positively influenced. To this end, they investigated samples of brain tissue from deceased patients, cell cultures and mice with a genetic disposition for PSP.  ‘We found that the disease sequelae decrease when PERK is activated with pharmaceuticals,’ [Hoglinger said.]  ‘Therefore, the protein could be a starting point for the development of new drugs.'”

The short article is copied below.

Robin

——————————

www.sciencedaily.com/releases/2017/02/170206103407.htm

Science News
A protein called PERK may be a target for treating progressive supranuclear palsy
Acting upon the maintenance system of neurons alleviates disease sequelae in laboratory experiments

Date:  February 6, 2017
Source:  DZNE – German Center for Neurodegenerative Diseases

Summary:
The brain disease ‘progressive supranuclear palsy’ (PSP) is currently incurable and its symptoms can only be eased to a very limited degree. PSP impairs eye movements, locomotion, balance control, and speech. Scientists have now discovered a molecular mechanism that may help in the search for effective treatments.

FULL STORY
The brain disease “progressive supranuclear palsy” (PSP) is currently incurable and its symptoms can only be eased to a very limited degree. PSP impairs eye movements, locomotion, balance control, and speech. Scientists at the German Center for Neurodegenerative Diseases (DZNE) and the Technical University of Munich (TUM) have now discovered a molecular mechanism that may help in the search for effective treatments. Their study focusses on a protein called PERK (protein kinase RNA-like endoplasmic reticulum kinase). A team of researchers led by Prof. Günter Höglinger reports on this in the journal EMBO Molecular Medicine.

PSP belongs to a group of neurological diseases referred to as “tauopathies.” In these diseases, a molecule called “tau” forms clumps rather than stabilizing the cytoskeleton as it normally does. Affected neurons can degenerate or even perish. To prevent such events, pathological molecules are normally repaired or disposed of by the organism. The protein PERK is part of such a maintenance system. However, in PSP, this mechanism appears to be defective. In previous studies, Höglinger and his colleagues had found that the risk for PSP is associated with variants at the PERK gene, and that loss of PERK function induces tau pathology in humans. For the current study, they examined the functioning of this protein more closely, to see how its effects could be positively influenced. To this end, they investigated samples of brain tissue from deceased patients, cell cultures and mice with a genetic disposition for PSP.

“We found that the disease sequelae decrease when PERK is activated with pharmaceuticals. That is to say: when its effect is enhanced,” says Höglinger, who leads a research group at the DZNE’s Munich site. “These results are still basic research and far from being ready for use in patients. However, our investigations show that PERK is an important part of the disease mechanism. Therefore, the protein could be a starting point for the development of new drugs.”

Höglinger also sees potential for tackling diseases other than PSP. This is because PERK helps eliminate abnormal tau molecules, and these also occur in other brain diseases. “These results could have a broad relevance. Because defective tau molecules play an important role especially in Alzheimer’s disease,” the researcher says.

Journal Reference:
Julius Bruch, Hong Xu, Thomas W Rösler, Anderson De Andrade, Peer‐Hendrik Kuhn, Stefan F Lichtenthaler, Thomas Arzberger, Konstanze F Winklhofer, Ulrich Müller, Günter U Höglinger. PERK activation mitigates tau pathology in vitro and in vivo. EMBO Molecular Medicine, 2017; e201606664 DOI: 10.15252/emmm.201606664

“Next-Generation Tau PET Tracers Strut Their Stuff” – differentiating PSP from AD

This is a report by Alzforum from the Alzheimer’s/Parkinson’s 2017 conference in Vienna at the end of March.  The focus of the report is on next-generation tau PET tracers.  Tau is the protein involved in Alzheimer’s Disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick’s disease, and chronic traumatic encephalopathy.

There are five new PET tracers under development.  The report says:

“[The] new tracers…appear at first glance to be able to overcome the limitations of the earlier compounds. In general, the newcomers boast higher brain uptake and more specific binding, yielding cleaner-looking scans with sharper distinction between positive and negative findings. While the older tracers work only in AD, some of the new ones appear to light up other tauopathies, as well. Researchers at Piramal Imaging wowed the crowd with scans showing a distinct, specific pattern of binding of their tracer in progressive supranuclear palsy (PSP) compared to AD.”  (Check out the online version of the article for AD vs. PSP images.)

The first-generation tau PET tracers described in the report are:  Lilly/Avid’s AV-1451 (flortaucipir) and THK5351, discovered at Tohoku University in Sendai, Japan, and licensed by GE Healthcare for commercial distribution.  The report indicates that both tracers have lots of problems.

As a result, many researchers are “now eyeing Merck’s and Piramal’s [tracers]. … Merck reported on their tau PET tracer, MK-6240, at the Human Amyloid Imaging (HAI) meeting held January.”  Other companies working on tau ligands include Genentech, Roche, and Janssen.

“Piramal started a Phase 1 trial on four people with AD, three with PSP, and two healthy controls. … Notably, AD and PSP scans revealed distinct patterns. In PSP, only a few discrete regions, mainly the pallidum and substantia nigra, lit up. In contrast, AD patients took up tracer in broader areas known to accumulate tau tangles, such as the lateral temporal lobe, hippocampus, entorhinal cortex, and precuneus.  Curiously, one of the AD patients had a negative tau scan. Stephens noted this patient had mild AD, with an MMSE of 26, and may not have accumulated much pathological tau yet. Incidentally, other PET experts, too, noted that as more research groups image both amyloid and tau pathology in the same cognitively impaired people, they are finding a few whose scans are amyloid-positive but tau-negative.”

Here’s a link to the full report:

www.alzforum.org/news/conference-coverage/next-generation-tau-pet-tracers-strut-their-stuff

Next-Generation Tau PET Tracers Strut Their Stuff
Series – AD/PD 2107 Draws Record Number of Scientists To Vienna
14 Apr 2017
by Alzforum

Robin

 

FTD Disorders Registry is now live

The FTD Disorders Registry is an online database to collect information from those affected by all types of Frontotemporal Degeneration: behavioral variant FTD (bvFTD), any one of the primary progressive aphasias (PPA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or FTD with motor neuron disease (also called FTD-ALS). Persons diagnosed, caregivers (current/former), family, and friends can join and tell your story.

Brain Support Network encourages all those affected by PSP and CBD to join the registry.

www.ftdregistry.org

Even if your family member has passed away, you can still join the registry and tell your story.

Robin

Excerpts on PSP and CBD in “The Dementias” (NIH online-only booklet)

This email may be of interest to those dealing with the dementia forms of PSP and CBD.  (Not everyone with these diseases has dementia.  To read about the types of PSP and CBD, look under the “PSP Education” and “CBD Education” pages of the Brain Support Network website.)

The National Institutes of Health (nih.gov) has several publications on neurological diseases.  I recently came across their booklet on “The Dementias,” which includes a section on tauopathies as types of dementia.  Tauopathies are caused by the abnormal accumulation of the protein tau.  Both corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are covered.  Other tauopathies addressed include frontotemporal disorders (such as Pick’s) and argyrophilic grain disease (AGD).  (In brain donations we’ve helped with, AGD co-occurs in about 20% of all PSP cases.)

“The Dementias” booklet links to the NIH pages on CBD and PSP.  I think the PSP detail page is quite good (and it’s listed as one of our “Top Resources for PSP”).  I don’t think the CBD detail page is nearly as good.

Here are excerpts from the tauopathies section.  Look at the booklet online for other chapters — risk factors, diagnosis and treatment, etc. — and other types of dementia.

Robin

————————–

nia.nih.gov/alzheimers/publication/dementias/types-dementia

Excerpts from

The Dementias
NIH Online Booklet
Published September 2013 (Last Updated July 2016)

Types of Dementia

Various disorders and factors contribute to the development of dementia. Neurodegenerative disorders such as AD, frontotemporal disorders, and Lewy body dementia result in a progressive and irreversible loss of neurons and brain functions. Currently, there are no cures for these progressive neurodegenerative disorders.

Some types of dementia disorders are described below.

Tauopathies

In some dementias, a protein called tau clumps together inside nerve cells in the brain, causing the cells to stop functioning properly and die. Disorders that are associated with an accumulation of tau are called tauopathies.

In AD, the tau protein becomes twisted and aggregates to form bundles, called neurofibrillary tangles, inside the neurons. Abnormal clumps (plaques) of another protein, called amyloid, are prominent in spaces between brain cells and are a hallmark of the disease. Both plaques and tangles are thought to contribute to reduced function and nerve-cell death in AD, but scientists do not fully understand this relationship. It is not clear, for example, if the plaques and tangles cause the disorder, or if their presence flags some other process that leads to neuronal death in AD.

Other types of tauopathies include the following disorders:

Corticobasal degeneration (CBD) is a progressive neurological disorder characterized by nerve-cell loss and atrophy (shrinkage) of specific areas of the brain, including the cerebral cortex and the basal ganglia. The disorder tends to progress gradually, with the onset of early symptoms around age 60. At first, one side of the body is affected more than the other side, but as the disease progresses both sides become impaired. An individual may have difficulty using one hand, or one’s hand may develop an abnormal position.

Other signs and symptoms may include memory loss; trouble making familiar, focused movements (apraxia) such as brushing one’s teeth; involuntary muscular jerks (myoclonus) and involuntary muscle contractions (dystonia); alien limb, in which the person feels as though a limb is being controlled by a force other than oneself; muscle rigidity (resistance to imposed movement); postural instability; and difficulty swallowing (dysphagia). People with CBD also may have visual-spatial problems that make it difficult to interpret visual information, such as the distance between objects.

There is no cure for CBD. Supportive therapies are available to reduce the burden of certain symptoms. For example, botulinum toxin can help control muscle contractions. Speech therapy and physical therapy may help one learn how to cope with daily activities.

Frontotemporal disorders (FTD) are caused by a family of brain diseases that primarily affect the frontal and temporal lobes of the brain; they account for up to 10 percent of all dementia cases. Some, but not all, forms of FTD are considered tauopathies. In some cases, FTD is associated with mutations in the gene for tau (MAPT), and tau aggregates are present. However, other forms of FTD are associated with aggregates of the protein TDP-43, a mutated protein found among people with a type of ALS that is inherited. Mutations in a protein called progranulin may also play a role in some TDP43-opathies.

In FTD, changes to nerve cells in the brain’s frontal lobes affect the ability to reason and make decisions, prioritize and multitask, act appropriately, and control movement. Some people decline rapidly over 2 to 3 years, while others show only minimal changes for many years. People can live with frontotemporal disorders for 2 to 10 years, sometimes longer, but it is difficult to predict the time course for an affected individual. In some cases, FTD is associated with progressive neuromuscular weakness otherwise known as amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). The signs and symptoms may vary greatly among individuals as different parts of the brain are affected. No treatment that can cure or reverse FTD is currently available.

Clinically, FTD is classified into two main types of syndromes:

* Behavioral variant frontotemporal dementia causes a person to undergo behavior and personality changes. People with this disorder may do impulsive things that are out of character, such as steal or be rude to others. They may engage in repetitive behavior (such as singing, clapping, or echoing another person’s speech). They may overeat compulsively; lose inhibitions, causing them to say or do inappropriate things (sometimes sexual in nature); or become apathetic and experience excessive sleepiness. While they may be cognitively impaired, their memory may stay relatively intact.

* Primary progressive aphasia (PPA) causes a person to have trouble with expressive and receptive speaking—finding and/or expressing thoughts and/or words. Sometimes a person with PPA cannot name common objects. Problems with memory, reasoning, and judgment are not apparent at first but can develop and progress over time. PPA is a language disorder not to be confused with the aphasia that can result from a stroke. Many people with PPA, though not all, develop symptoms of dementia. In one form of PPA, called semantic PPA or semantic dementia, a person slowly loses the ability to understand single words and sometimes to recognize the faces of familiar people and common objects.

Other types of FTDs include:

* Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a rare form of dementia that is believed to be inherited from one parent and is linked to a defect in the gene that makes the tau protein. The three core features are behavioral and personality changes, cognitive impairment, and motor symptoms. People with this type of FTD often have delusions, hallucinations, and slowness of movement and tremor as seen in Parkinson’s disease. Typical behavioral/personality characteristics include apathy, defective judgment, and compulsive and abusive behavior. Diagnosis of the disorder requires the confirmed presence of clinical features and genetic analysis. Palliative and symptomatic treatments such as physical therapy are the mainstays of management.

* Pick’s disease, a tauopathy subtype of FTD characterized by hallmark Pick bodies—masses comprised of tau protein that accumulate inside nerve cells, causing them to appear enlarged or balloon-like. Some of the symptoms of this rare neurodegenerative disorder are similar to those of AD, including loss of speech, inappropriate behavior, and trouble with thinking. However, while inappropriate behavior characterizes the early stages of Pick’s disease, memory loss is often the first symptom of AD. Antidepressants and antipsychotics can control some of the behavioral symptoms of Pick’s disease, but no treatment is available to stop the disease from progressing.

Progressive supranuclear palsy (PSP) is a rare brain disorder that damages the upper brain stem, including the substantia nigra (a movement control center in the midbrain). This region also is affected in Parkinson’s disease, which may explain an overlap in motor symptoms shared by these disorders. Eye movements are especially affected, causing slow and then limited mobility of the eye. The most common early signs and symptoms include loss of balance, unexplained falls, general body stiffness, apathy, and depression. A person with this type of dementia may suddenly laugh or cry very easily (known as pseudobulbar affect). As the disorder progresses, people develop blurred vision and a characteristic vacant stare that involves loss of facial expression. Speech usually becomes slurred, and swallowing solid foods or liquids becomes difficult. PSP gets progressively worse, but people can live a decade or more after the onset of symptoms. Dextromethorphan, a common ingredient in cough medicine, has been approved for the treatment of pseudobulbar affect.

Argyrophilic grain disease is a common, late-onset degenerative disease characterized by tau deposits called argyrophilic grains in brain regions involved in memory and emotion. The disease’s signs and symptoms are indistinguishable from late-onset AD. Confirmation of the diagnosis can be made only at autopsy.

Multimodal Imaging Ties Tau to Neurodegeneration, and Symptoms

This is an Alzforum (alzforum.org) article about important researcher into tauopathies by researchers at Mass General.  The article was posted last week to Alzforum; the research study was published online in JAMA Neurology a couple of weeks ago.

What the researchers confirmed is that there is a “tight correlation between tau neurofibrillary tangles and neurodegeneration in individual patients in early clinical stages of various forms of Alzheimer’s disease.”  Three patients with typical Alzheimer’s Disease (AD) were studies, and three patients with atypical AD were studied.  One of the “atypical AD” cases was a person with corticobasal syndrome (CBS)

In this study, all patients were given a tau PET scan, an amyloid PET scan, and an MRI.  Researchers found that “tau predicts atrophy [which] predicts symptoms.”  It is not the protein amyloid in the brain that predicts atrophy or predicts symptoms.

In fact, we have known this from brain donation for a long time but now researchers have confirmed this in living patients.

Perhaps one reason that a CBS patient was studied rather than a PSP (progressive supranuclear palsy) patient is that the tau load in CBD is greater than in PSP.

Here’s a link to the article:

www.alzforum.org/news/research-news/multimodal-imaging-ties-tau-neurodegeneration-and-symptoms

Multimodal Imaging Ties Tau to Neurodegeneration, and Symptoms
Alzforum
07 Mar 2017

It is challenging reading.  Check it out online for cool images of the patient with corticobasal syndrome.

Robin

“We Will Go On” Blog by Dan Brooks

My longtime friend Dan Brooks in Riverside reactivated his blog “We Will Go On” in 2016 and moved it to wewillgoon.com.  Dan’s blog has the tagline:

Parkinsonism: Hard to Diagnose.  Harder to live with. 
A blog by a patient with Parkinsonism Plus Syndrome.

In 2006, Dan was diagnosed with multiple system atrophy (MSA), corticobasal syndrome (CBS), and progressive supranuclear palsy (PSP).  As time went on, MSA became the most likely.  It seems that CBS has come back into the picture, however.

Dan recently posted about the confusion over whether he has Parkinson’s Disease, CBS, and MSA.  I’ve copied his post below.

Robin

————————-

www.wewillgoon.com/2017/03/confusion-over-parkinsons-contrasted.html

Confusion Over Parkinson’s Contrasted with CBS and MSA
by Dan Brooks
Saturday, March 4, 2017

I have quite often discussed with some of you in the family, and various friends, about the difference between Parkinson’s Disease and the Atypical Parkinsonian disorders.  I am going to give you a few points to chew on, knowing you are the best ambassadors we have for spreading the word about these rarer forms of Parkinsonism.

Parkinsonism is a condition in which signs and symptoms of Parkinson’s appear in the patient’s disease.  Even though the person may not have Parkinson’s Disease, they have a brain disorder that causes similarly appearing symptoms, including tremors, balance problems, stiffness, walking difficulty and cognitive changes.

Parkinsonism appears with Parkinson’s Plus syndromes such as Multiple System Atrophy, Corticobasal Syndrome and Progressive Supranuclear Palsy.  Since I was first diagnosed in 2006, the neurologist I saw for ten years thought that my condition was one of these three.  As time went on, Multiple System Atrophy became the most likely.  All three of these conditions are determined to be “probable” in life, and are confirmed after death through a brain tissue study.

Even though I have  Parkinsonism it is not Parkinson’s Disease in the simplest form because the disease process in my brain is more involved than in Parkinson’s.  I have Corticobasal Syndrome (CBS), and it is uncertain if it would be alternatively considered Multiple System Atrophy (MSA).  These have overlapping symptoms and are best described as rarer forms of Parkinson’s.

Has much changed?  Not really, except I have more clarity and certainty of the degenerative brain disease that has taken so much from our lives in the Brooks family.  We are fortunate to have this increased clarity because the neurologist I have been seeing of late is a Movement Disorder specialist, which is a doctor of Neurology who specializes in all things Parkinson’s and Parkinson’s-like.   She saw a clear indication in the results of my DaT Scan which demonstrated that I have Parkinson’s Plus, not simply Parkinson’s Disease.

Parkinson’s Plus has long been the understanding of my condition.  I wrote about this in my book, I WILL GO ON: LIVING WITH A MOVEMENT DISORDER.  The confusion arises because the word “Parkinson’s” appears in both descriptions of the diseases.  Technically, they are different in that Parkinson’s Plus is a faster progressing disease and causes more disability sooner.

That is why I was unable to continue driving and had to retire at 51.  I have difficulty walking with coordination and I struggle with choking on food and liquids.  I also have digestive, urinary, heart rate, blood pressure regulation and body temperature issues.  These are not visible to friends and family so what appears to be a better day, could be a day I am having trouble with my blood pressure or having great difficulty coughing after drinking liquids.

I also have very abnormal horizontal eye movements which are caused by a loss of neurons in the area of the brain that controls eye movement.  At times I see double as a result.

I am so glad that you are interested and are trying to grow in your knowledge.  MSA is a disease I have been identified with for 10 years or more.  I have CBS, but if it were to turn out to be MSA at some point, that would be a very similar prognosis. My greatest concerns are pneumonia, breathing constriction, and urinary infections.  I do not have idiopathic Parkinson’s, but I do have a form of Parkinsonism, and much of the research being done for P.D. will have a benefit and weight heavily on the potential for discoveries that relate to PSP, MSA and CBS syndromes.  I will always identify with my fellow patients who have Parkinson’s Disease, and the support groups for Parkinson’s are virtually the only in person, brick and mortar groups we can attend anywhere near the Riverside, CA area. As always, thanks for reading! — Patient-Online