Pheno Therapeutics Ltd. has received clinical trial authorization (CTA) from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for its lead candidate, PTD-802. The program will progress to a first-in-human phase I trial.
The differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes (OLs) promotes the remyelination in human brain. In multiple sclerosis (MS), dysfunctional OPC differentiation leads to remyelination failure and subsequent severe neurological disability.
High extracellular glutamate levels damage axons, myelin and oligodendrocytes in the context of inflammatory demyelinating disorders such as multiple sclerosis (MS).
To date, therapies for multiple sclerosis (MS) focus on modifying or suppressing the immune system rather than on remyelination. Recent findings have pointed to the κ-opioid receptor (KOR) as a therapeutic target for remyelination, but several KOR agonists have undesired side effects that limit their use. Researchers from the Victoria University of Wellington have tested KOR agonists derived from U-50488 in the preclinical setting for the management of MS.
Semaphorin 3A signaling, through the plexin A1/neuropilin 1 (PLXA1/NRP1) receptor complex, is known to disrupt the differentiation and migration of oligodendrocyte precursor cells and mature remyelinating oligodendrocytes. Both semaphorin 3A and plexin A1 are up-regulated in the central nervous system of patients with multiple sclerosis.
In multiple sclerosis (MS), macrophages and microglia play a dual role that could be used to treat this neurodegenerative disease. These cells promote inflammation that demyelinates neurons but also sweep away the debris of damaged myelin and produce neurotrophic factors that would allow its restoration. According to a group of scientists from the University of Hasselt in Belgium, damage or repair depends on a double switch that combines the action of two enzymes, one that desaturates and another that elongates fatty acids. By reducing the levels of these enzymes, phagocytic cells would replenish the myelin instead of engulfing it.
For many multiple sclerosis patients, the approval over the past 30 years of a lengthy list of immunomodulatory therapies has helped to reduce the frequency of relapses and to slow disease progression. However, there has been little parallel progress in the development of remyelination therapies, to tackle the other key pathophysiological dimension of the disease. Patients still have no therapies that can help to repair at least some of the damage that results from flare-ups, and the resulting neuronal loss contributes to further disease progression and disability. Rewind Therapeutics NV, of Leuven, Belgium, is one of a small clutch of firms attempting to tackle this problem.
Pipeline Therapeutics Inc., which received U.S. FDA approval to move into a phase Ib/IIa study of PIPE-307 in relapsing-remitting multiple sclerosis (RRMS) last year, will be advancing the oral, small-molecule muscarinic M1 receptor antagonist in collaboration with Janssen Pharmaceutica NV in an agreement that could be worth more than $1 billion.
Researchers from Georgetown University presented data from a study that aimed to assess the intrinsic mechanisms by which myeloid cells regulate their activation states during remyelination and to identify new therapeutic targets for multiple sclerosis (MS).
It was previously demonstrated that the CNS-penetrant compound bryostatin-1 (bryo-1) exerts an immunomodulatory effect on myeloid-lineage innate immune cells in the periphery through its actions on protein kinase C (PKC). In a new study, researchers from Johns Hopkins University aimed to assess the potential of bryo-1 for the treatment of progressive multiple sclerosis (MS) by investigating its effect on remyelination.
