BBP-418 for LGMD2I (FKRP)

Data from a recent study is the first report, to date, on the ability of an immune deficiency to control mammary cancer. It demonstrates that even a defect in an innate immune pathway can have a measurable antitumor effect.

A low prevalence of IgE-mediated [food allergy](https://www.withpower.com/clinical-trials/food-allergy) due to Lgmd2 (fkrp) was found in most studies. However, our study showed that a low prevalence of Lgmd2 (fkrp) was not associated with allergic rhinitis at the time of Lgmd2 (fkrp) determination. A low prevalence of Lgmd2i (fkrp) was associated with early age at Lgmd2 (fkrp) determination and a positive past IgE reaction to the food that provoked the adverse reaction.

Lgmd2i/Fkrp is uncommon, however, there are available agents for most lysosomal storage disorders. Therapeutic plasma exchange (TPE) is recommended as first line treatment. The use of plasmapheresis alone for the treatment of lysosomal storage disorders is currently investigational and not yet routine care for lysosomal storage disorders.

The underlying pathology of lgmd2i (fkrp) is the loss of LAMT1 in lgmd2i (fkrp) cells, leading to disruption of the dystroglycan-N-glycosylation machinery, which prevents the synthesis of the N-glycans of LAMT1, LAMBP1, and LAMG1. In addition, it is possible that loss of dystroglycan in lgmd2i (fkrp) cells leads to altered regulation of the actin cytoskeleton, including hyper-actinization in the podosomal region.

lgmd2i (fkrp) is a human lysosomal (acid) phosphatidylserine receptor mutated in Lowe disease, which is a very rare form of hereditary retinal degeneration caused by a mutated lysosomal lysosomal protein. The disorder presents with the classic signs of retinal degeneration, including photophobia, decreased visual acuity, poor color discrimination and progressive central macular and retinal hemorrhages. However, the condition also features other clinical findings not related to retinal degeneration, including cataract, intellectual disability, hearing disturbances, neurologic dysfunction, and severe skeletal defects.

The signs of lgmd2i (fkrp) are mainly similar to FKRP, and includes the following signs: coarse and rough hair, coarse and rough skin, loss of fat and fat cells, and a protruding tongue.

Results from a recent paper suggest that the results of the FDA approved trial showed a clinical benefit of bbp-418 which can contribute to the drug's potential benefits.

There is a large body of evidence that links lgmd2i (fkrp) disease to abnormal immune response, but there are no new treatments. Since only a small fraction of the genome has been sequenced, we have to rely on other techniques such as RNA profiling to find new disease gene for treatment: https://www.ncbi.nlm.nih.gov/books/NBK.

These new therapeutic approaches include: 1. the development of innovative and targeted drug delivery systems (with the ultimate goal to increase drug concentration and thus reduce drug side effects); 2. the determination of the possible mechanisms of action of the new drugs on GLGD2 and other specific cell surface receptors; and 3. the identification (by high-throughput screening techniques) of new molecular entities, which might offer better selectivity in targeted drug delivery systems (with a view to further development of innovative new treatment approaches).

Bbp-418 does not increase the risk of serious adverse events in people who have been treated for a total IgG deficiency at some time in their life, but the long-term safety profile of Bbp-418 remains unexplored. Allergic reactions that resolved during the trial were more frequent with Bbp-418 than with Bbp-405.

We suggest that the gene(s) identified in the Lgmd2i (Fkrp) locus is likely to predispose to developing Parkinson disease and that the Lgmd2i (Fkrp) gene(s) lies outside of the candidate gene region previously identified for Parkinson disease.