BioWire Weekly - 011

Biotech News

Happy Tuesday Evening, Readers.

This week’s edition of BioWire will cover a number of interesting topics including HIV therapeutics, longevity/lifespan, Lupus, and Alzheimer'sDisease.

Seventh Person Cured of HIV with Gene Therapy

A seventh person, dubbed "The Next Berlin Patient," has been seemingly cured of HIV following a hematopoietic stem cell transplant to treat acute myeloid leukemia. The patient received donor cells with the heterozygous delta-32 CCR5 mutation, which imparts partial resistance to HIV. This case, with nearly six years of follow-up, suggests potential for gene therapies targeting HIV, even when a functional receptor is present, and gives hopes for broader HIV cures (Read more here).

Extending lifespan by targeting IL-11

Figure shows a Kaplan-Meiers survival curve for WT vs IL-11 knockout mice (a-c) and WT mice treated with a control or anti-IL-11 antibodies (d-f). Average survival time increases with removal of IL-11.

Longevity therapeutics relating to lifespan (the total length lived) and healthspan (the duration of high quality of life) continue to be emerging interest within the biotech space. Several targets for age-related diseases are emerging. A recent study published in Nature discovered that inhibiting IL-11 signaling can extend both the healthspan and lifespan in mice. The research demonstrated that deletion of IL-11 or its receptor (Il11ra1) in mice protected against age-related metabolic decline, multi-morbidity, and frailty. Administering anti-IL-11 antibodies to aged mice improved metabolism and muscle function and reduced aging biomarkers. The findings suggest that targeting IL-11 could be a promising strategy for mitigating age-associated diseases and extending lifespan in humans (Widjaja et al, 2024).

Discovery of a Lupus Cause and Potential Reversal

Researchers have discovered that a defect in the aryl hydrocarbon receptor (AHR) pathway plays a critical role in lupus, an autoimmune disease where the immune system attacks healthy tissues. In lupus patients, there is an imbalance between two types of T cells: CXCL13+ T cells, which promote inflammation, and IL-22+ T cells, which help protect tissues. The study found that interferon, a protein that boosts the immune response, disrupts this balance by increasing the number of inflammatory CXCL13+ T cells.

Using CRISPR technology to delete the AHR gene in T cells, scientists observed an increase in CXCL13 production and a decrease in IL-22, indicating that AHR naturally inhibits the production of inflammatory cells. By blocking the AHR pathway, researchers could potentially restore the balance between these T cell types, reducing inflammation and the severity of lupus symptoms.

This discovery suggests that targeting the AHR pathway could be a new therapeutic approach for lupus, offering hope for more effective treatments with fewer side effects than current options (Law et al, 2024).

Nasal Delivery of Tau Antibody Shows Promise for Treating Neurodegenerative Diseases

Previously, we have discussed the shortcomings of the amyloid plaque theory of Alzheimer’s disease. An alternative theory indicates intracellular Tau could be a contributor to this disease. In a recent study, scientists developed a monoclonal antibody called TTCM2 that targets toxic tau oligomers associated with Alzheimer’s disease (Meftah et al, 2024). Traditionally, tau-targeting therapies have struggled to reach neurons in the brain due to the blood-brain barrier. However, the researchers overcame this obstacle by packaging TTCM2 in micelles and delivering it intranasally, allowing the antibody to bypass the blood-brain barrier and directly enter the brain through the nasal mucosa.

In mouse models of tauopathy, a single intranasal dose of the TTCM2-loaded micelles led to significant reductions in tau pathology and improvements in cognitive functions. The study demonstrated that TTCM2 specifically binds to tau oligomers, preventing their toxic effects and their spread between neurons. This binding triggers the TRIM21 pathway, an intracellular mechanism that degrades the tau-antibody complex, further reducing tau levels in the brain.

This approach of using micelles as a vehicle to enhance the lipophilicity of the antibody and delivering it via the nasal route provides a non-invasive, efficient way to target neurodegenerative diseases. While this study was conducted in mice, it opens up the potential for similar therapies in humans, pending further research and clinical trials. This method could represent a glimmer of hope in a depressingly stagnant Alzheimer’s field.

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References:

Law, C., Wacleche, V.S., Cao, Y., Pillai, A., Sowerby, J., Hancock, B., Horisberger, A., Bracero, S., Skidanova, V., Li, Z. and Adejoorin, I., 2024. Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus. Nature, pp.1-10.

Meftah, S., Durrant, C.S. and Spires-Jones, T.L., 2024. A nose for tau. Science Translational Medicine, 16(754), p.eadq6489.

Widjaja, A.A., Lim, W.W., Viswanathan, S., Chothani, S., Corden, B., Dasan, C.M., Goh, J.W.T., Lim, R., Singh, B.K., Tan, J. and Pua, C.J., 2024. Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature, pp.1-9.