Progressive Supranuclear Palsy: Medications and Promising New Trials

Progressive Supranuclear Palsy: Medications and Promising New Trials

Progressive supranuclear palsy (PSP) is a rare neurological condition that affects movement, balance, speech, vision, and cognition. It is caused by the degeneration of brain cells, leading to an accumulation of a protein called tau. PSP shares similar symptoms with Parkinson's disease, but it progresses more rapidly and typically has a poorer prognosis.

There is currently no cure for PSP, and treatments mainly focus on managing symptoms and improving the quality of life for patients. However, researchers are continuously exploring new medications and clinical trials to find more effective treatments. This blog post will delve into the medications currently used to manage PSP and highlight some promising clinical trials that offer hope for the future.

Current Medications for PSP

  1. Levodopa

Levodopa is a medication used to manage Parkinson's disease, and it has also been used to treat the motor symptoms of PSP. Levodopa is converted into dopamine in the brain, which helps regulate movement. Unfortunately, levodopa has limited effectiveness in PSP patients, as it often provides only mild and temporary relief from symptoms.

  1. Antidepressants

Depression is a common non-motor symptom in PSP patients. Antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, can help alleviate depressive symptoms and improve the quality of life. Common SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), while examples of tricyclic antidepressants are amitriptyline and nortriptyline.

  1. Anticholinergics

Anticholinergic medications can help manage some of the movement-related symptoms of PSP by blocking the action of acetylcholine, a neurotransmitter involved in muscle contractions. However, these medications can cause side effects like dry mouth, blurred vision, and constipation, making them less suitable for long-term use. Examples of anticholinergics are trihexyphenidyl (Artane) and benztropine (Cogentin).

  1. Botulinum toxin

Botulinum toxin injections, commonly known as Botox, can help manage involuntary eye closure (blepharospasm) and other eye movement disorders in PSP patients. The toxin works by temporarily paralyzing the muscles responsible for these involuntary movements.

  1. Amantadine

Amantadine is an antiviral medication that may help alleviate some of the motor symptoms of PSP, such as rigidity and bradykinesia (slow movement). However, its effectiveness is limited, and it may cause side effects like insomnia, dizziness, and hallucinations.

Promising Clinical Trials for PSP

Despite the limitations of current medications, there is reason to be hopeful about future treatment options for PSP. Several clinical trials are underway to investigate the safety and efficacy of new drugs that target the underlying causes of the disease. Some of the most promising clinical trials include:

  1. ABBV-8E12 (Taucilizumab)

ABBV-8E12 is a humanized monoclonal antibody that targets the abnormal tau protein. The drug aims to prevent the accumulation of tau in the brain, which could potentially slow the progression of PSP. A Phase 2 clinical trial of ABBV-8E12 (NCT03068468) showed encouraging results, and a Phase 3 trial (NCT04270489) is currently underway to further evaluate the safety and efficacy of the drug in PSP patients.

  1. Anle138b

Anle138b is a small molecule that has been shown to reduce the accumulation of tau protein in preclinical studies. It is believed to work by blocking the aggregation of tau, thereby preventing the formation of toxic protein deposits in the brain. A Phase 1 clinical trial (NCT04558462) has been completed to evaluate the safety, tolerability, and pharmacokinetics of Anle138b in healthy volunteers. The results of this trial will determine whether Anle138b will progress to further clinical testing in PSP patients.

  1. PRX002/RG7935 (Semorinemab)

PRX002/RG7935 is another monoclonal antibody that targets tau protein, with the aim of reducing its accumulation in the brain. A Phase 2 clinical trial (NCT03100149) known as the PASADENA study was conducted to evaluate the safety and efficacy of PRX002/RG7935 in patients with early Parkinson's disease. Although the trial did not meet its primary endpoint, secondary endpoints showed some positive trends, which may warrant further investigation of the drug in PSP and other tauopathies.

  1. BIIB092 (Gosuranemab)

BIIB092 is a monoclonal antibody that binds to extracellular tau, preventing the spread of tau pathology between brain cells. The drug has shown promise in preclinical studies and has been tested in a Phase 2 clinical trial (NCT03688972) for PSP patients. Unfortunately, the trial did not meet its primary endpoint, but further analysis of the data may provide insights that could guide the development of future tau-targeting therapies.

  1. Nilotinib

Nilotinib is a tyrosine kinase inhibitor that is currently approved for the treatment of certain types of leukemia. Preclinical studies have suggested that nilotinib may also have neuroprotective effects by promoting the clearance of toxic proteins, including tau, from the brain. A Phase 2 clinical trial (NCT02947893) was conducted to evaluate the safety and efficacy of nilotinib in patients with Parkinson's disease and dementia with Lewy bodies. While the trial did not meet its primary endpoint, it did show some positive trends, which may encourage further investigation of nilotinib in PSP and other neurodegenerative disorders.

While there is currently no cure for progressive supranuclear palsy, ongoing research and clinical trials offer hope for the development of more effective treatments in the future. Current medications can provide some symptom relief and improve the quality of life for PSP patients, but they do not address the underlying cause of the disease. The clinical trials mentioned in this post represent just a few examples of the many research efforts aimed at finding new ways to target the pathological processes that drive PSP. As our understanding of the disease continues to grow, so too does the potential for breakthroughs that could significantly improve the lives of those affected by this devastating condition.

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38 comments

My mother in law now bedridden since 8 years with PSP now has seizures lasting 3 to 5 minutes ,2weeks apart .Interestingly after a post ictal phase of deep sleep of a 12 hours she then is very expressive,articulates speaks relevantly with good recall as if the seizure in itself was D.B.S.(-Deep brain stimulation as given in Parkinson’s desease) jogging her degenerating neurons to function well giving us a window of around 2 days while this last to communicate with her before she is back to her usual rigid seldom communicative self.
Would be glad to have feedback whether it makes sense to give her anti-epileptics that further obtund her already failing senses .She is presently only on Syndopa 125 mg tid & in her 14 th year post diagnosis, bedridden and the only challenge being feeding her crushed food slowly over an hour each time & finger defecation once in 4 days

Dr Conrad

Clinicaltrials.gov is where you find current trials for PSP. You can see if there are any in your area. Good luck all. This is a tough diagnosis. Participating in a trial gives hope.

Kathy Bettles

Hello Chuck,

I’m truly sorry to hear about your diagnosis. Progressive supranuclear palsy (PSP) can be a challenging condition to face, especially since you’ve been so healthy before. It’s important to have a strong support system and access to resources that can help manage the symptoms and challenges associated with PSP.

One organization dedicated to this cause is CurePSP. They are based in the USA and focus on providing information, support, and assistance to those affected by PSP, CBD (corticobasal degeneration), and MSA (multiple system atrophy). Here’s how CurePSP can assist you:

1. Information and Education: CurePSP offers a wealth of resources on understanding the disease, managing symptoms, and coping strategies. They provide educational materials that can help you and your loved ones comprehend various aspects of PSP.

2. Support Groups: CurePSP connects patients and their families with support groups, where you can meet others facing similar challenges. These support networks can be invaluable for emotional support, practical advice, and reassurance that you’re not alone in this journey.

3. Healthcare Communication Assistance: They can guide you on effectively communicating with your healthcare team, ensuring you’re well-prepared for appointments, and understand how to describe symptoms or side effects you’re experiencing.

4. Events and Programs: CurePSP organizes events, webinars, and programs that focus on educating, raising awareness, and fostering a community among those affected by these rare conditions. Participating could provide you with additional support and information.

You can reach CurePSP through their website or contact them directly for personalized assistance. They are committed to supporting patients and families during such challenging times. www.PSP.org

Remember, while CurePSP provides excellent support and resources, maintaining regular contact with your healthcare professionals is crucial for managing your symptoms and adapting to life with PSP. They can offer medical advice, therapy options, and ongoing care tailored to your specific needs.

Hugs xx

Laura Louizos

I am Chuck. I am 73 and never have been sick. I was diagnosed with progressive supranuclear palsy at the Cleveland Clinic. Help me!

Chuck Morrison

My mums neurologist has said he believes she has PSP, she has all the symptoms other than the swallowing difficulties, she can’t keep her eyes open ( the Botox isn’t helping either) , and she falls all the time, can’t sleep, etc I would love to know if she is eligible! It’s so so hard watching her deteriorate! We are in Sydney Australia

Lisa Vassallo

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