Novel treatment of neurodegenerative diseases by altering levels of TrkB isoforms and/or TrkC isoforms
AssigneeUniversity of Maryland, Baltimore
InventorsBruce K. Krueger, Tami J. Kingsbury, Linda L. Bambrick, Susan G. Dorsey
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Abstract
This invention relates to a method of treating or preventing neuro-degenerative disorders and neuro-developmental disorders by altering the ratio of the amount of full-length TrkB polypeptide to the amount of truncated TrkB polypeptides in a neuron or by altering the ratio of the amount of full-length TrkC polypeptide to the amount of truncated TrkC polypeptides in a neuron.
Claims54
A method of treating a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding full-length TrkB or any mutant, variant, homolog, or fragment thereof having the same activity as said full-length TrkB, whereby said amount of said isolated nucleic acid is sufficient to increase the amount of full-length TrkB in neurons compared to untreated neurons.
A method of preventing a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding full-length TrkB or any mutant, variant, homolog, or fragment thereof having the same activity as said full-length TrkB, whereby said amount of said isolated nucleic acid is sufficient to increase the amount of full-length TrkB in neurons compared to untreated neurons.
A method of treating a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding anti-sense RNA for a truncated TrkB isoform, whereby said amount of said isolated nucleic acid is sufficient to decrease the amount of truncated TrkB in neurons compared to untreated neurons.
A method of preventing a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding anti-sense RNA for a truncated TrkB isoform, whereby said amount of said isolated nucleic acid is sufficient to decrease the amount of truncated TrkB in neurons compared to untreated neurons.
A method of inhibiting the progression of a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising
- administering an amount of a vector to said mammal whereby said amount of said vector is sufficient to alter the ratio of amount of full-length TrkB polypeptide to truncated TrkB polypeptide in a neuron, and whereby said vector comprises an isolated nucleic acid.
A method for treating a disease in a mammal characterized by an increased ratio of the amount of truncated TrkB polypeptides to the amount of full-length TrkB polypeptide in a cell as compared to said ratio in a healthy mammal, said method comprising
- administering an amount of a vector to said mammal whereby said amount of said vector is sufficient to alter said ratio of amount of truncated TrkB polypeptide to the amount of full-length TrkB polypeptide in said cell, and whereby said vector comprises an isolated nucleic acid.
A method of treating a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding full-length TrkC or any mutant, variant, homolog, or fragment thereof having the same activity as said full-length TrkC, whereby said amount of said isolated nucleic acid is sufficient to increase the amount of full-length TrkC in neurons compared to untreated neurons.
A method of preventing a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding full-length TrkC or any mutant, variant, homolog, or fragment thereof having the same activity as said full-length TrkC, whereby said amount of said isolated nucleic acid is sufficient to increase the amount of full-length TrkC in neurons compared to untreated neurons.
A method of treating a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding anti-sense RNA for a truncated TrkC isoform, whereby said amount of said isolated nucleic acid is sufficient to decrease the amount of truncated TrkC in neurons compared to untreated neurons.
A method of preventing a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising:
- administering to said mammal an amount of an isolated nucleic acid encoding anti-sense RNA for a truncated TrkC isoform, whereby said amount of said isolated nucleic acid is sufficient to decrease the amount of truncated TrkC in neurons compared to untreated neurons.
A method of inhibiting the progression of a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising
- administering an amount of a vector to said mammal whereby said amount of said vector is sufficient to alter the ratio of amount of full-length TrkC polypeptide to truncated TrkC polypeptide in a neuron, and whereby said vector comprises an isolated nucleic acid.
A method for treating a disease in a mammal characterized by an increased ratio of the amount of truncated TrkC polypeptides to the amount of full-length TrkC polypeptide in a cell as compared to said ratio in a healthy mammal, said method comprising
- administering an amount of a vector to said mammal whereby said amount of said vector is sufficient to alter said ratio of amount of truncated TrkC polypeptide to the amount of full-length TrkC polypeptide in said cell, and whereby said vector comprises an isolated nucleic acid.
A method of inhibiting the progression of a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising
- administering an amount of a polypeptide encoded by a nucleic acid encoding full-length TrkB, or any mutant, variant, homolog, or fragment thereof having the same activity as full-length TrkB, whereby said amount of said polypeptide increases the amount of full-length TrkB in a neuron.
A method of inhibiting the progression of a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising
- administering an amount of a polypeptide encoded by a nucleic acid encoding full-length TrkC, or any mutant, variant, homolog, or fragment thereof having the same activity as full-length TrkC, whereby said amount of said polypeptide increases the amount of full-length TrkC in a neuron.
A method of inhibiting the progression of a neuro-degenerative disorder or a neuro-developmental disorder in a mammal, said method comprising
- administering an amount of the combination of a first polypeptide encoded by a nucleic acid encoding full-length TrkB, or any mutant, variant, homolog, or fragment thereof having the same activity as full-length TrkB, whereby said amount of said first polypeptide increases the amount of full-length TrkB in a neuron and a second polypeptide encoded by a nucleic acid encoding full-length TrkC, or any mutant, variant, homolog, or fragment thereof having the same activity as full-length TrkC, whereby said amount of said second polypeptide increases the amount of full-length TrkC in a neuron.
A pharmaceutical composition comprising
- a vector comprised of polynucleotide encoding for full-length TrkB polypeptide wherein said full-length TrkB polypeptide has the sequence in SEQ ID NO:
- 2;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- a vector comprised of polynucleotide encoding for full-length TrkC polypeptide wherein said full-length TrkC polypeptide has the sequence in SEQ ID NO:
- 10;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- a vector comprised of polynucleotide encoding for anti-sense RNA specific for a truncated TrkB isoform;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- a vector comprised of polynucleotide encoding for anti-sense RNA specific for a truncated TrkC isoform;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- a vector comprised of polynucleotide encoding for double-stranded RNA specific for a truncated TrkB isoform;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising
- a vector comprised of polynucleotide encoding for double-stranded RNA specific for a truncated TrkC isoform;
- and
- a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.