In the Cannacord analysis report it say's this about regulus...

In the Cannacord analysis report it say's this about regulus approach to APKD Verses PYC

Its targeting approaches are very different, with PYC targeting a much more
upstream mutation of the disease pathway, while RGLS targets a more downstream
gene that is upregulated in kidney cysts.

I am no medico by a long shot ! and needed the help of Chat GPT to help me out, below is the result...... I think it's telling me we get the chance to cure it and Regulus get chance to manage it.

In treatingAutosomal Dominant Polycystic Kidney Disease (ADPKD), targeting an upstreammutation of the disease pathway versus targeting downstream effects can lead todifferent therapeutic outcomes. Here are the significant differences:

TargetingUpstream Mutations

1. GeneticCorrection:

• Approach: This involves correcting the specific genetic mutations (PKD1 or PKD2) that cause ADPKD.

• Methods: Techniques like CRISPR/Cas9 gene editing, antisense oligonucleotides, or RNA interference can be used to correct or silence the mutant gene.

• Advantages:

• Potential for Cure: By correcting the root cause, there is a potential for a more definitive and long-lasting solution.

• Preventionof Disease Progression: Early intervention can prevent or significantly delay the onset and progression of cyst formation and kidney dysfunction.

• Challenges:

• Delivery: Efficiently delivering gene-editing tools to kidney cells is challenging.

• Safety: Risks include off-target effects and immune responses.

• Technical Complexity: The precision required for editing or silencing specific genes without affecting other cellular functions.

2. PathwayInhibition:

• Approach: This involves inhibiting the molecular pathways activated by the mutant proteins produced by PKD1 or PKD2 mutations.

• Methods: Small molecules or monoclonal antibodies can be used to inhibit these pathways.

• Advantages:

• Broad Impact: Inhibiting upstream pathways can affect multiple downstream processes, potentially reducing cyst growth and preserving kidney function.

• Challenges:

• Complexity of Pathways: The pathways involved are complex and interconnected, making targeted inhibition difficult.

• SideEffects: Inhibiting upstream pathways can affect normal cellular functions, leading to side effects.

TargetingDownstream Effects

1. SymptomManagement:

• Approach: This involves treating the symptoms and complications resulting from cyst growth and kidney dysfunction.

• Methods: Medications to manage pain, hypertension, and other symptoms, along with dialysis or kidney transplantation for end-stage renal disease.

• Advantages:

• Symptom Relief: Directly addresses patient discomfort and improves quality of life.

• ExistingTreatments: Many symptom management therapies are already available and well-studied.

• Challenges:

• No Cure: This approach does not address the underlying cause and only manages symptoms.

• DiseaseProgression: Cyst growth and kidney damage continue, leading to eventual kidney failure.

2. CystReduction:

• Approach: This involves reducing the size and number of cysts formed in the kidneys.

• Methods: Use of vasopressin V2 receptor antagonists, mTOR inhibitors, or other agents that can reduce cyst growth.

• Advantages:

• Targeted Therapy: Directly targets cysts to reduce kidney damage and preserve function.

• DiseaseManagement: Slows disease progression and delays the need for dialysis or transplantation.

• Challenges:

• Partial Efficacy: May not completely stop cyst growth, only slowing progression.

• SideEffects: Potential for adverse effects due to the drugs used.

Summary

• UpstreamTargeting: Aims for a potential cure by addressing the root genetic causes but faces significant technical and safety challenges.

• DownstreamTargeting: Focuses on managing symptoms and reducing cyst growth, which can improve quality of life and delay disease progression but does not cure the disease.

Acombination of both approaches might offer the most comprehensive strategy fortreating ADPKD, addressing both the genetic causes and the symptomatic effectsof the disease.