Prothena and Celgene to Work Together on ALS Therapies

Prothena and Celgene are teaming up to develop treatments for a range of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).

The collaboration will focus on therapies that can target proteins such as tau and TDP-43 that scientists have linked to these disorders.

“The programs we have chosen to collaborate on have the potential to provide foundational assets from which we can build new therapeutic approaches to these currently untreatable neurological disorders,” Richard Hargreaves, Celgene’s corporate vice president of neuroscience and imaging, said in a press release.

Tau is believed to play a role in Alzheimer’s disease and frontotemporal dementia. Scientists think TDP-43 is involved in ALS.

Prothena has created TDP-43-related antibodies that could be used to treat ALS. It is using a proprietary laboratory screening technique to identify which antibodies could do the best job of inhibiting the toxicity of misfolded TDP-43 and its cell-to-cell transmission. Misfolded TDP-43 is essentially a faulty version of the protein.

A number of studies have suggested that focusing on TDP-43 could lead to a treatment for ALS.

Just this month, Canadian scientists discovered how TDP-43 interacts with the hnRNP A1 RNA sequence to promote ALS.

When TDP-43 binds with the sequence, it leads to the production of a longer version of the protein, researchers discovered. Not only does the elongated protein accumulate in ALS patients’ nerve cells, but it also forms toxic clumps that may contribute to the disease’s progression, researchers said.

Earlier studies showed that TDP-43 by itself was not enough to trigger ALS. The Canadian researchers identified the molecule that interacted with TDP-43 as the hnRNP A1 protein.

They also discovered that people with ALS have higher levels of the longer version of the hnRNP A1 protein in their movement nerve cells. This abnormal accumulation correlated with levels of dysfunctional TDP-43.

These discoveries could open up new pathways for treating the disease.

The team reported on its findings in an article in the journal Brain titled “TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis.”

Under the Prothena-Celgene agreement, Celgene will give Prothena $100 million up-front and buy $50 million worth of Prothena stock. Prothena can obtain additional payments by meeting certain goals.

Celgene gets the right to license therapies the partners develop for the U.S. market.