Antibody-depends Neurological Disease Solutions

The understanding of mechanism and intervention for various neurological diseases have greatly expanded in recent years. In addition to research on molecular mechanisms, many more targeted disease mitigation methods have also been developed. These include a range of antibody-based therapies such as single-chain fragment variable (scFv), single-domain antibody fragments, bispecific antibodies, in vivo antibodies and Nabs. Most of them are in preclinical research and development, and a small number are entering the clinical stage for testing as potential treatments. With our excellent R&D team, Creative Biolabs now provides reliable, comprehensive and flexible one-stop neurological disease solutions targeting variable antibodies.

Huntington's Disease (HD)

With the deepening of the understanding of the pathogenesis of HD, antibody therapy against the free form of mHtt has also entered the development stage. Although experimental data on antisense oligonucleotides (AOS) for the intervention of such diseases are promising, targeting mHtt as an ideal target also has prospective implications and some benefits, as peripheral mHtt burden affects the immune system and transmits pathology, and mHtt's Prion-like behavior also has clinical implications.

Fig 1. Antibody targets for Htt/mHtt. (Denis, 2019)

At present, antibody therapy for HD is mainly carried out through several modes of action, including directly binding to the functional domain of the target protein, targeting different subcellular compartments, or direct introduction of prefabricated antibodies into the body through passive immunization and providing immediate protection for patients.

Alzheimer's Disease (AD)

Hallmark pathological findings of AD include extracellular accumulation of Aβ and intracellular neurofibrillary tangles resulting from hyperphosphorylated tau. There is also substantial genetic and pathological evidence that Aβ is a viable drug target in AD, which has led to a number of promising AD antibody therapies, including,

• Using anti-BACE1 to reduce Aβ production
• Removing amyloid via Anti-Aβ treatment
• Slowing the spreading of tau pathology with anti-tau antibodies.

Fig 2. Antibody approaches and mechanisms of AD. (Yu, 2013)

Prion Diseases

Prion disease is a fatal neurological disease caused by a pathological itch-related form of normal cellular prion protein. Many studies have proved that prion-carrying Nab and in vivo antibodies can prevent the toxicity of PrPc and the formation of PrPSc, but there are still few studies in animal models. In addition, anti-PrPSc drugs have also been shown to significantly prolong latency, with no inflammatory and neurotoxic effects observed. Another promising target for preventing prion disease is the cell-surface receptor for the non-integrin laminin receptor, which has seen better molecular effects in animal experiments, but did not result in significantly longer survival in mice.

Synucleinopathies

Abnormal accumulation and dissemination of synuclein in the central and peripheral systems and formation of Lewy bodies or glial cytoplasmic inclusions are observed in synucleinopathies including Parkinson's disease, Lewy Body dementia, and Multiple Sclerosis. Over the years, researchers have developed specific antibodies that can attenuate the accumulation of aggregated α-syn and associated pathology within TCM in a nuclear preclinical model of synucleinopathies. In addition to this, there are also approximately 50 synucleinopathic antibodies under research and development.

Myasthenia Gravis (MG)

MG is an autoimmune neuromuscular disease characterized by antibodies to the nicotinic acetylcholine receptor, which produces disabling frailty by impairing neuromuscular transmission. MG has several feasible and reasonable therapeutic targets, including B cell activator, CD40 activator, complement inhibitor, and antibody circulatory system inhibition.

Fig 3. Pathophysiology and therapeutic targets of myasthenia gravis. (Alabbad, 2020)

Other Diseases

In addition to some common and well-studied diseases, Creative Biolabs also provides one-stop modalities services for other types of neurological diseases, including,

• Neurodegenerative Disorders
• Neuromuscular Disorders
• Psychiatric Disorders
• Pain
• Rare Diseases
• Brain Tumors
• Ophthalmology

We also offer BBB Shuttle Antibody Therapy Development Service for customer all over the world. If you wish to learn more about these diseases, develop and validate antibody therapies or have other needs, please do not hesitate to contact us for more details.

References

1. Denis, H.I.; et al. Antibody-based therapies for Huntington’s disease: current status and future directions. Neurobiology of Disease. 2017, 132: 104569.
2. Yu, Y.J.; Watts, R.J. Developing therapeutic antibodies for neurodegenerative disease. Neurotherapeutics. 2013, 10: 459-472.
3. Alabbad, S.; et al. Monoclonal antibody‑based therapies for myasthenia gravis. Biodrugs. 2020, 34: 557-566.