This blog post from 2013 is about the hummingbird sign and Mickey mouse sign in progressive supranuclear palsy (PSP). These are “signs” on an MRI. I had heard of the hummingbird sign previously but not the Mickey mouse sign. MRI images are shown.
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)
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
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:
As always, I’ve deleted the deep brain stimulation-related talks.
Half Moon Bay
Thursday, 6/1, 3-4pm
Guest Speaker: Cherry Tuck, PD fighter
Topic: Her journey
San Jose/Willow Glen
Friday, 6/2, 10am-noon (program starts about 10:20am)
Program: Break into two groups — those with PD and caregivers
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
Monday, 6/5, 10-11am
Guest Speaker: Dianna Powell, San Joaquin County coordinator, Legal Services of Northern California
Topic: HICAP and Medicare updates
Tuesday, 6/6, 1:30-3pm
Guest Speaker: Saul Avila, Acadia Pharmaceuticals
Topic: Nuplazid – new drug for psychosis and schizophrenia associated with Parkinson’s
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
Wednesday, 6/7, 1:30-3pm
Guest Speaker: Attorney, Corporon Law Offices
Topic: Long-term care planning (trusts, wills, and other legal documents)
Thursday, 6/8, 10-11am
Guest Speaker: Vanessa Kettler, balance instructor
Topic: Balance and fall prevention
Thursday, 6/8, 1:30-3pm
Guest Speaker: Christopher Trinchera
Topic: Medical marijuana
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
Saturday, 6/10, 10am-noon
Guest Speaker: Beate Ritz, MD, PhD, UCLA
Topic: PEG (Parkinson’s, Environment & Genes) study at UCLA
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
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
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
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]
Wednesday, 6/14, 1-2pm
Guest Speaker: Robert McCulla, DDS, dentist
Topic: Parkinson’s and sleep
Wednesday, 6/14, 2-3:30pm
Guest Speaker: Ellen Corman, manager, Farewell to Falls, Stanford Health Care
Topic: Fall prevention in Parkinson’s
Thursday, 6/15, 10am-noon
Guest Speaker: Lin Zhang, MD, PhD, movement disorder specialist, UC
Topic: PD – more than motor symptoms
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
Tuesday, 6/20, 10-11am
Guest Speaker: Millie Nunez, PD cycling instructor, Sun City Lincoln Hills
Topic: Nutrition and forced exercise
Tuesday, 6/20, 1:30-3pm
Guest Speaker: Stephanie Fiola, RN, AbbVie Pharmaceuticals
Topic: Discovering Duopa – carbidopa/levodopa eternal suspension
Wednesday, 6/21, 1:30-3:30pm
Guest Speaker: Carlos Becerra, personal trainer, Alpha Fitness
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
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
Monday, 6/26, 7-9:30pm
Guest Speaker: Han Lee, MD, movement disorder specialist, Kaiser San Leandro
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:
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.
Michael J. Fox Foundation Webpage
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:
* 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.
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:
(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.
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
* 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
– Pelvic floor exercises
– Limit fluids/caffeine, schedule bathroom breaks, use incontinence aids
– Medication to relax the bladder
– Botulinum toxin injections
Difficulty eliminating urine
– Medication to stimulate bladder emptying
– Evaluate current drugs to ensure none contribute (e.g., Artane/trihexiphenidyl)
– 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.
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.
There are two Interesting articles in today’s Economist magazine (economist.com) that report on the “huge gap between what people want from end-of-life care and what they are likely.” This gap was found in a survey done by The Economist in partnership with the Kaiser Family Foundation. For the survey, people in the US, Brazil, Italy and Japan were asked a set of questions about dying and end-of-life care.
Here’s a link to the first article, which is actually a short editorial by the magazine:
How to have a better death
Death is inevitable. A bad death is not
Economist, Print edition
Apr 29th 2017
It cites two statistics:
* Nearly a third of Americans who die after 65 will have spent time in an intensive-care unit in their final three months of life.
* Almost a fifth undergo surgery in their last month.
Here’s a link to the second article:
A better way to care for the dying
How the medical profession is starting to move beyond fighting death to easing it
Economist International Edition
Apr 29th 2017
The second article, titled “A better way to care for the dying,” addresses what Atul Gawande, MD, calls “the experiment of making mortality a medical experience.” It cites a few statistics:
* People in rich countries can spend eight to ten years seriously ill at the end of life.
* Many deaths are preceded by a surge of treatment, often pointless. Nearly a third of elderly Americans undergo surgery during their final year; 8% do so in their last week.
* By 2020, 40% of Americans are expected to die alone in nursing homes.
* One international review of prognoses of patients who die within two months suggests that seriously ill people live on average little more than half as long as their doctors suggested they would. Another study found that, for patients who died within four weeks of receiving a prognosis, doctors had predicted the date to within a week in just a quarter of cases. Mostly, they had erred on the side of optimism.
* Remarkably, in three trials the patients receiving palliative care lived longer, even though the quantity of conventional treatment they opted to receive was lower.
* In one study just 43% of people who had written living wills wanted the same treatment course two years later.
Both articles are worth reading.
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.
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
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.
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.
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
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:
Next-Generation Tau PET Tracers Strut Their Stuff
Series – AD/PD 2107 Draws Record Number of Scientists To Vienna
14 Apr 2017
This announcement has been updated as of April 12, 2017:
Brain Support Network is pleased to announce the establishment of the Allan Marcus Fund for Families in Need with PSP. The Fund has been created in loving memory of Allan, whose diagnosis of progressive supranuclear palsy (PSP) was confirmed through brain donation after his passing in 2016. His family wishes to help PSP families — through grants of up to $1500 — to enrich or celebrate their loved one in a special way.
The grant program is specifically open to those with a family member with clinically diagnosed PSP who live in the US. Applictions will be considered starting May 15, 2017.
A grant will be considered for costs or activities that would otherwise not be financially feasible. Ideas for use of the grant include (but are not limited to) therapy, travel, or creation of meaningful events or memories with your loved one.
Download the fund overview and application in PDF.
Questions? Please email Mindy Lumm, Secretary of Brain Support Network.
I received this email on Sunday from Storme, one of the founding members of our local progressive supranuclear palsy (PSP) support group:
You’ve probably already heard this, but I was watching last week’s “Chicago Med,” and one of the patients had PSP! Her diagnosis was sort of secondary to her personal story; she was afraid her boyfriend would vamoose upon learning she would “lose swallowing, speech and brain function.” So nothing especially helpful, but I was pleased to hear it mentioned on a popularly-watched TV show nonetheless.