Treatment of Parkinson's disease: what's on the horizon?

[Farooqji]

Many companies are trying to bring Parkinson's disease treatments to the market. These include

1. Acorda Therapeutics, Inc.'s Inbrija,

2. Prothena Corporation plc's PRX002

3. AstraZeneca's MEDI1341

4. Edison Pharma's Vatiquinone

5. Prexton Therapeutics' Foliglurax

6. Prana Biotechnology's PBT434.

7. Biogen's BIIB054

8. ISC's stem cell trial "ISC-hpNSC"

A lot has been happening in the space lately.

[Astra7]

I hope they hurry up!

[jeeves19]

Which of these would be the most fruitful and why?

[Farooqji in reply to jeeves19]

A lot of potential is there in No. 2 and 8

[Farooqji]

Progress on Parkinson’s

The charity Parkinson’s UK summarises the state of play for drug treatments for Parkinson’s disease pretty succinctly. “Current medications can help to manage Parkinson’s symptoms, but we don’t yet have any treatments that can cure, slow, stop or reverse the progression.” In short, there is an urgent medical need for more effective drugs. My father had Parkinson’s, so I know how debilitating it is and that experience makes me particularly keen to see the development of an effective treatment. Some of the companies mentioned above in connection with Alzheimer’s also have clinical trials of new Parkinson’s treatments in progress, as do some other large pharmaceutical companies.

For example, Prothena, a US biotech, has partnered with Roche on PRX002 for Parkinson’s which is in Phase II trials, while drugs giant Pfizer also has a Phase II trial in progress for Parkinson’s. At earlier stages of development, we have biotech group Biogen, whose BIIB054 is in Phase I clinical trials, and AstraZeneca’s MEDI1341, which is about to enter Phase I clinical trials on Parkinson’s patients and has just been partnered with Japanese drugmaker Takeda to co-develop it.

An example of a risky-but-promising biotech approach to Parkinson’s comes from Voyager Therapeutics. The motor symptoms associated with Parkinson’s disease, such as shaking and slow movement, are caused by falling levels of the neurotransmitter dopamine in the putamen, an area of the brain that helps to regulate motion. This in turn is caused by the death of dopamine neurons in a part of the brain called the substantia nigra, which is where a substance called levodopa is converted into dopamine, which is then released into the putamen. This reaction is catalysed by an enzyme called AADC for short.

Giving Parkinson’s patients doses of levodopa can help to offset this, but as the disease becomes more advanced, levodopa becomes less effective and adverse effects increase. And around 15% of Parkinson’s patients, says Voyager, have motor fluctuations that are not well controlled by levodopa. In both cases, Voyager’s VY-AADC01 gene therapy (see page 24) is designed to help. This therapy delivers the AADC gene directly into neurons of the putamen (which are not damaged by Parkinson’s). This enables those neurons to express the AADC enzyme, which in turn means that levodopa can be converted into dopamine directly in the putamen, effectively cutting out the substantia nigra altogether. Voyager still has almost no revenue, but it has announced positive results for a Phase Ib trial of the treatment, which “demonstrated durable dose-dependent and time-dependent improvements across multiple measures of patients’ motor function after administration of the gene therapy”.