The Future of Parkinson’s Disease Treatments – What’s New?

New Parkinson’s Disease Treatments in the Pipeline

The pipeline for new Parkinson’s disease (PD) medications is very crowded, with multiple new medications in various stages of research development that are targeting neuroprotection, as well as motor and non-motor symptoms. In several past blogs we have reviewed many strategies currently being tested for PD, which you can review below:

• Neuroprotective strategies in clinical trials
• Neuroprotective strategies in clinical trials – update
• Therapies for non-motor symptoms in clinical trials

Thankfully, the PD research landscape is always changing with new treatments and opportunities being explored, so there are now some additional potential compounds that are in clinical trials for PD we want to tell you about along with why researchers think that they might be beneficial. You can read more about each of the clinical trials mentioned below by following the links provided. You will find these and many other PD trials listed on clinicaltrials.gov, a database of all the clinical trials for all diseases worldwide.

New Parkinson’s Medication on the Horizon

There are so many potential medications that are being researched that it is hard, even for scientists and physicians who study Parkinson’s disease, to know about all of them. Thankfully Dr. Kevin McFarthing, a former biochemist and person with Parkinson’s, has created The Parkinson’s Hope List — a collation of all the compounds that are being explored as new therapies for PD at all stages of the research pipeline and is updated frequently. It is an excellent source of information for those interested in the current state of PD research focused on new potential treatments. APDA was privileged to recently host Dr. McFarthing as a special guest on our broadcast entitled Dr. Gilbert Hosts: Taking Research From the Lab to our Lives.

As a review, below are the main treatment strategies that researchers are focused on:

• Targeting abnormal alpha-synuclein aggregation which is thought to play a key role in degeneration of nerve cells in PD
• Decreasing inflammation in the brain that could contribute to PD pathology
• Improving function of the mitochondria – the energy-producing element of the nerve cell – to support the health of the neurons
• Increasing the activity of the nerve cell’s lysosomal or garbage disposal system to enhance destruction of cellular debris that could damage the cell
• Decreasing activity of the proteins LRRK2 or c-Abl to decrease neurodegeneration
• Increasing neurotrophic factors to enhance nerve survival

Here are some additional compounds that have shown promise in the treatment of PD and are currently in clinical trials:

1. Anavex 2-73 activates a molecule in the nerve cells called the Sigma-1 receptor. This receptor is involved in many functions in the cell including the decrease of inflammation, and enhancement of nerve cell survival and growth. Activation of this receptor is thought to restore health to nerve cells by lowering toxic accumulation of misfolded protein and enhancing response to oxidative stress.
   A phase 2 trial was completed in the fall of 2021 and after 14 weeks of testing demonstrated significant improvement in cognitive measures as well as a statistically significant and clinically meaningful reduction in motor symptoms of PD. Results have not been published yet in a peer-reviewed journal. The next step will be for the scientific community to review the results once they are published. A larger phase 3 trial would then hopefully be planned.
2. Tak-071 is a molecule that increases the activity of the muscarinic receptor. This is a type of receptor that interacts with the brain chemical acetylcholine, which along with dopamine, plays a vital role in the motor systems that are affected in Parkinson’s disease. Acetylcholine also plays a key role in both cognition and control of balance and gait.
   Tak-071 is currently being studied in a clinical trial for people with PD who have cognitive impairment to determine if it leads to an improvement in walking and cognition.
3. Dipraglurant is a molecule that decreases the activity of the glutamate receptor and is being studied for its ability to reduce levodopa-induced dyskinesias (LIDs). LIDs are rapid, involuntary, and uncontrollable movements (other than tremor) that can develop as a side effect of levodopa in those with moderate to advanced PD. LIDs appear as body swaying, twisting, or writhing. Dipraglurant showed a statistically significant reduction in LIDs in a published double-blinded, placebo-controlled phase 2 study.
   It is currently being tested in a larger phase 2b/3 study.
4. NE3107 is a molecule that binds to a well-studied enzyme within the cell called ERK (extracellular signal-regulated kinase). ERK is known to plays a major role in brain inflammation. When it is activated, it also causes insulin resistance, which means that it inhibits the ability of cells to respond properly to insulin. If cells can’t respond to insulin, they can’t use glucose properly as an energy source which can contribute to cell death.
   A phase 2 study is now underway, testing NE3107 in people with PD who are currently on levodopa.
5. CVN424 is a molecule that decreases the activity of a receptor in the brain called the G-protein-coupled receptor member 6 (GPCR6). GPCR6 has been shown to play a role in the brain pathways that are over-active in PD and decreasing its activity with CVN424 improved motor function in animal models of PD. The molecule was well tolerated in a recently completed phase I study in healthy volunteers.
   A phase 2 study in people with PD with motor fluctuations is now underway.
6. CNM-Au8 is a suspension of gold nanoparticles. Research has shown that gold nanoparticles enter the brain and act to drive metabolic energy reactions, increasing the amount of energy that the cells can produce, which leads to healthier cells.
   A pilot study was conducted with CNM-Au8 to assess the brain metabolic effects of this compound in people with PD.  A phase 2 study will get underway this year.
7. WIN-1001X is a plant extract from three plant species used in Chinese medicine – Polygala tenuifolia, used to improve cognition, Angelica tenuissima, used for a wide array of medical conditions including headaches and epilepsy, and Dimocarpus longan, used for general health. WIN-1001X showed beneficial effects in mouse models of PD and is currently being evaluated in a phase 2 trial for its effects on motor symptoms in people with early PD.

Tips and Takeaways

• The scientific community remains focused on finding new treatments for Parkinson’s disease and the continual addition of new compounds being studied and developed is exciting news for the PD community.
• In addition to those mentioned above, you can read about a number of other strategies currently being studied in our prior blogs which you can access here and here.
• APDA funds cutting-edge pre-clinical work which is vital for discovering the compounds that can be tested in clinical trials. Check out what we fund.