Unlocking the Therapeutic Potential of Tmem100 Peptides for Advanced Disease Treatment

Introduction

The potential for peptide-based therapies in modern medicine continues to grow, offering unique and highly specific treatment options for various diseases. Tmem100, a membrane-associated protein, has emerged as a key player in several critical physiological processes, making it an ideal target for developing new therapies. Our patented technology centers on Tmem100 peptides and their variants, providing a groundbreaking opportunity to treat or prevent a variety of conditions, including chronic pain, cancer, and cardiovascular diseases.

Current Gaps in Targeted Therapeutics

While modern medicine has made great strides in addressing chronic diseases, many current treatments lack specificity, leading to unwanted side effects and incomplete symptom relief. Conditions such as chronic pain are often treated with opioids or non-specific pain relievers, which can carry risks of dependency and systemic side effects. Similarly, cancer therapies may target cells broadly, affecting healthy tissues as well as malignant ones, limiting the effectiveness and tolerability of treatment. The need for targeted therapies that modulate specific pathways at a molecular level is clear, especially for conditions involving complex cellular processes.

The Precision of Tmem100 Peptide Therapy

Our patented Tmem100 peptides and their variants offer a highly specific approach to targeting key molecular pathways involved in various diseases. Tmem100 plays a crucial role in several physiological mechanisms, including ion channel regulation, which is relevant for pain modulation and certain cardiovascular conditions. By designing peptides that modulate Tmem100 activity, we can develop therapies that offer more precise targeting of disease-related pathways, potentially reducing side effects while increasing therapeutic efficacy.

These peptides and their variants are not limited to a single therapeutic area. This technology has the potential to impact a wide range of conditions, from pain management to cancer treatment. Tmem100 modulation can also be applied in the cardiovascular space, providing new avenues for treating heart-related conditions through a peptide-based approach.

Key Advantages of This Technology

Targeted Mechanism of Action: By focusing on Tmem100, this peptide-based approach allows for more precise therapeutic targeting, reducing side effects while enhancing efficacy.
Broad Therapeutic Applications: This technology can be applied to multiple disease areas, including chronic pain, cancer, and cardiovascular conditions.
Reduced Side Effects: Peptide-based therapies often provide a higher degree of specificity, potentially leading to fewer adverse reactions compared to traditional drugs.
Versatility in Treatment: These Tmem100 peptides and variants offer potential use in both prevention and treatment, expanding the scope of their application in clinical settings.

A Key Opportunity for Cutting-Edge Therapeutics

Licensing this Tmem100 peptide technology offers pharmaceutical companies and biotech firms an exceptional opportunity to lead in the development of next-generation, peptide-based treatments. As the demand for more targeted, effective therapies grows, this technology opens the door to breakthroughs in multiple disease areas, offering the chance to significantly improve patient outcomes with precision-driven care.

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Abstract
Claims

The present invention features compositions of Tmem100 peptides and variants thereof, and their use in treating or preventing diseases or conditions.

What is claimed is:

1. A method for treating or preventing a condition associated with TRPA1 function or for which reduced TRPA1 activity can reduce the severity, comprising administering an effective amount of a Tmem100 mutant polypeptide, comprising administering to the cell an effective amount of a Tmem100 mutant polypeptide, wherein the Tmem100 mutant polypeptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 17, thereby inhibiting TRPA1 function in the cell; or

a method of preventing, treating, or alleviating symptoms of a disease or condition associated with TRPA1 function or for which reduced TRPA1 activity can reduce the severity, comprising administering to a subject in need thereof a Tmem100 mutant polypeptide, wherein the Tmem100 mutant polypeptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 17, thereby inhibiting TRPA1 function in the cell; or

a method of inhibiting TRPA1 function in a cell, comprising administering to the cell an effective amount of a Tmem100 mutant polypeptide, wherein the Tmem100 mutant polypeptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 17, thereby inhibiting TRPA1 function in the cell.

2. The method of claim 1 wherein the TRPA1 function is an association with TRPV1.

3. The method of claim 2, wherein the Tmem100 mutant polypeptide enhances the association of TRPA1 with TRPV1.

4. The method of claim 1, wherein said TRPA1 function is an inward TRPA1-mediated current, an outward TRPA1-mediated current, TRPA1-mediated ion flux or TRPA1-mediated neuronal hyperexcitability.

5. The method of claim 1, wherein the Tmem100 mutant polypeptide comprises a polypeptide with one or more alterations in the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 wherein the one or more alterations in the amino acid sequences enhance association of TRPA1 and TRPV1 and inhibit TRPA 1.

6. The method of claim 1, wherein the Tmem100 mutant polypeptide is provided to a cell and the cell is a sensory neuron.

7. The method of claim 6, wherein the cell body of the sensory neuron resides in the dorsal root ganglia (DRG).

8. The method of claim 1, used to prevent, treat, or alleviate symptoms of pain.

9. The method of claim 1, used to prevent, treat, or alleviate symptoms of itch.

10. The method of claim 8, wherein the pain is acute pain or chronic pain.

11. The method of claim 1, wherein the Tmem100 mutant polypeptide is administered in combination with one or more agents.

12. The method of claim 1, wherein the Tmem100 mutant polypeptide is administered in combination with one or more of a TRPV1 inhibitor, a TRPV3 inhibitor, a TRPV4 inhibitor, or a TRPM8 inhibitor.

13. A pharmaceutical composition for treating or preventing a condition involving activation of TRPA1 or for which reduced TRPA1 activity can reduce the severity, comprising an effective amount of a Tmem100 mutant polypeptide, wherein the Tmem100 mutant polypeptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

14. The pharmaceutical composition of claim 13, wherein the Tmem100 mutant polypeptide comprises a polypeptide with one or more alterations in the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 wherein the one or more alterations in the amino acid sequences enhance association of TRPA1 and TRPV1 and inhibit TRPA1.

15. An isolated cell-permeable polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, wherein the polypeptide is myristoylated or palmitoylated at each N-terminus.

16. An expression vector, which replicates in at least one of a prokaryotic cell and eukaryotic cell, comprising:

an isolated nucleic acid comprising a nucleotide sequence selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12; or

expresses a polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

17. A cell comprising an expression vector which replicates in at least one of a prokaryotic cell and eukaryotic cell, comprising:

an isolated nucleic acid comprising a nucleotide sequence selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12; or

wherein the expression vector expresses a polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

18. A method comprising culturing a cell in a cell culture medium, the cell comprising an expression vector which replicates in at least one of a prokaryotic cell and eukaryotic cell, wherein the expression vector comprises: an isolated nucleic acid comprising a nucleotide sequence selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12; or comprises a nucleotide sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

Title

Tmem100 peptides and variants thereof and their use in treating or preventing diseases or conditions

Inventor(s)

Xinzhong Dong, Hao-Jui Weng

Assignee(s)

Johns Hopkins University

Patent #

11066455

Patent Date

July 20, 2021