Repurposed medications to treat Parkinson’s Disease
Repurposing medications is a process by which medications already approved by the Food and Drug Administration (FDA) for one reason are tested and shown to work for another purpose.
One great example of this is the use of Amantadine for Parkinson’s disease (PD). Amantadine was first approved for the prevention and treatment of signs and symptoms of influenza A infection. Later on, when patients with PD taking amantadine for the flu had improvement in PD symptoms, it was tested and approved for treatment of parkinsonian symptoms.
There are a number of existing medications which are currently being considered for use in Parkinson’s disease (PD) that are already approved for other indications. This is significant because it could lead to new treatment options for people with PD much sooner than if the drugs were being evaluated for the very first time. Today I will discuss these medications.
Getting FDA approval for a brand-new drug is a massive undertaking. It is a simpler process to expand the indication of an existing medication (that is to show that a medication that already works for one purpose, can now also work for another) as compared to gaining approval for a new medication. This is because an approved medication for Parkinson’s is a known quantity, with a well-established side effect profile. This shortens the process by which the drug is approved for the second purpose.
Testing an already approved medication for use in Parkinson’s
It is essential for clinical trials to be designed to test that the already approved medication is effective specifically for PD, and safe specifically for people with PD. People with PD have unique clinical features – for example, a tendency for blood pressure fluctuations – that may make a particular drug’s side effect profile more problematic for people with PD than the general population.
How does a medication approved for one indication become a possibility for treating Parkinson’s?
This jump may occur if pre-clinical research, that is, research that is done in cell culture or PD animal models, suggests that a known drug may have efficacy in PD. Just because a drug shows neuro-protective properties when placed in a cell culture or improves parkinsonian symptoms when given to a mouse, does not mean that this will translate into a clinically meaningful difference if taken by people with PD. Therefore, observations made in a lab must be confirmed in clinical trials.
Another method by which an approved medication may gain consideration for use in PD is through mining large databases of medical information. Through epidemiological data, it may be noted for example, that those who have been prescribed a particular medication (for something else) have lower rates of PD. This information may be intriguing, but is far from enough information to conclude that taking the medication caused the lower rates of PD. And even if the medication does directly contribute to lower rates of PD, there may be no clinical effect of taking the medication in people who already have PD. Therefore, any suggestion of a medication benefit for PD gleaned from epidemiological data must be tested in a clinical trial.
What is off-label use?
Off-label use refers to the practice of prescribing a drug for a purpose that is not one of its FDA-approved indications – that is, without enough data to convince the FDA that it works for the secondary purpose. For example, a medication approved for epilepsy may be used for pain control, or a medication approved for depression may be used to enhance sleep. This is deemed an acceptable practice, and is frequently done, but caution must be taken.
You may read about pre-clinical or epidemiological data that suggests that an already approved medication may help PD, and want your neurologists or primary care doctors to start you on this medication before a clinical trial is done in PD. This is completely understandable – why withhold a medication that may help?
However, one must nonetheless proceed with extreme caution. If a person with PD is already prescribed a medication for the approved indication, then it may be reasonable to have a conversation with your neurologist and/or primary care physician about the possibility of switching to the medication in question. For example, if someone with PD already takes a medication for high blood pressure and another high blood pressure medication is implicated in neuroprotection in PD, then it would be reasonable to consider switching to the other medication. However, there may be a reason that your doctor originally chose the first medication specifically for your condition and there may be reasons that you may not tolerate the second medication, so listen to your doctor if he/she feels that the switch is not in your best interest.
There may also be people with PD who are generally wary of changing their meds because of a tendency for side effects from new medications. For any of these reasons, it would be entirely reasonable not to switch and instead to wait for the clinical trial data to show whether the implicated medication truly works in PD.
For those who are not already prescribed a medication for the approved indication, I would caution against starting a new medication that has not yet been proven to work in PD. Every new medication can introduce unnecessary side effects and medication interactions that are not fully understood in the context of PD. It is much more prudent to wait for clinical trial results that show whether it is a medicine worth taking for PD.
Alternatively, consider joining the clinical trial that is testing the efficacy of the approved medication in PD disease. Then, you have access to the approved medication, are closely monitored for side effects, and your experience becomes part of the data that decides whether the medication is useful in PD.
Isradipine is an approved blood pressure medication which showed great promise in pre-clinical research and in a small clinical trial, for its ability to be a neuro-protective agent for PD. A large clinical trial was then conducted and engendered much hope that finally a neuro-protective agent for PD could be offered. Unfortunately, in the spring of 2019, the results of the clinical trial were fully analyzed and showed that isradipine did not offer neuroprotection. This was disappointing for the PD community and demonstrated the difficulty in trying to repurpose medications for PD. This is a good example of why it is best to wait for the clinical trial results.
Which approved medications are being tested in Parkinson’s?
Despite this, efforts to find approved medications that benefit people with PD continue. Below is a list of medications that are already approved for use in other conditions and are currently being tested for PD (this is not a complete list):
- Terazosin – This medication is currently used to treat enlargement of the prostate and is being studied as a neuroprotective medication for PD. A recent study was published which showed that the drug could prevent neuron loss in a number of PD model systems including cell culture, mice, rats and flies. To begin to investigate the effects of the drug in people with PD, the researchers analyzed databases of patients who took terazosin and determined that they had fewer PD diagnoses. Those who had PD and took terazosin had decreased PD-related complications and slower disease progression. This type of epidemiologic data is suggestive that there is a relationship between terazosin and PD but it remains to be seen whether if given to people who already have the diagnosis of PD, that it will have a clinical effect. In order to determine that, a clinical trial is planned.
- Ambroxol – This is a medication that is approved for mucous clearance from the respiratory system. Pre-clinical data showed that ambroxol acts to support the function of glucocerebrosidase (GBA), an important enzyme which breaks down unwanted cellular products. GBA mutation can lead to an increased risk for the development of PD, so supporting healthy GBA function is important to explore. Ambroxol is currently in clinical trials for PD dementia.
- Glucagon-like peptide-1 (GLP-1) agonists – Exenatide, Liraglutide and Lixisenatide are medications approved for use in diabetes. In pre-clinical work, there was evidence that this type of medication can be neuro-protective. A small clinical trial with exenatide showed that it moderately improved motor scores in PD patients off medication – which could either suggest that it is neuro-protective, or has a symptomatic effect that is long lasting. Larger trials are necessary to further explore the effect of exenatide in PD. Lixisenatide and liraglutide are currently in clinical trials for PD.
- Buspirone – This is a medication approved for anxiety and is currently in a clinical trial to see if it helps control levodopa-induced dyskinesias.
- Nilotinib – This medication is currently used for the treatment of chronic myelogenous leukemia, a blood cancer. Pre-clinical data suggested that it may induce regulated destruction of alpha-synuclein, the protein that is known to clump within PD neurons, thereby stopping the abnormal clumping and protecting the neurons. In a very small clinical trial, patients showed improvements in their clinical condition, but the trial did not have a control arm (that is, a comparison group of patients who did not receive the drug) and therefore left many clinicians skeptical of the results. A larger placebo-controlled clinical trial is currently underway.
We will be keeping an eye on these trials and remain hopeful that new treatment options will result from this research.
Tips and Takeaways
- Repurposed medications are medications that are already approved for one use and are then tested for use in another medical condition
- Many already-approved medications are currently being tested to see if they are useful for PD.
- A new clinical trial is necessary to prove that the approved medication works specifically for PD and does not cause side effects to which people with PD may be particularly sensitive
- Despite the fact that these medications can already be prescribed by a physician, best practice is to wait for clinical trial results specifically in PD.
- Always discuss all medication decisions with your neurologist.
- APDA provides a list of medications approved for use in PD, as well as a list of medications to avoid.